JP2002179727A - Sulfone derivative and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a sulfone derivative useful for simple production of various indanone derivatives. SOLUTION: This sulfone derivative is expressed by formula (1) (where R100 represents an alkyl group, an alkenyl group, an aryl group or an aralkyl group each containing an oxygen-functional group (these groups may have an oxygen atom, a nitrogen atom, a sulfur atom or a halogen atom, or a substituent group which may contain the above atom); R101 represents a polymer residue which may have a substituent group; and R102 and R103 each represents an alkyl group, an alkenyl group, an alkynyl group or an aralkyl group (these groups may have a substituent group).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a sulfonyl chloride having a novel polymer residue, a sulfone derivative having a polymer residue by reacting the sulfonyl chloride with an alcohol, and a method for producing the same. In particular, the present invention relates to a method for producing an indanone derivative having a novel polymer residue. The novel sulfonyl chloride having a polymer residue, the sulfone derivative having a polymer residue, and the method for producing the same according to the present invention include various derivatives of various physiologically active substances and synthetic methods, particularly various derivatives of vitamin D. And is useful for synthetic methods.

[0002]

2. Description of the Related Art Sulfonyl chloride having a polymer residue produces a sulfone derivative having a polymer residue by reaction with an alcohol. When various nucleophiles act on this sulfone derivative, various physiologically active substances can be synthesized at the same time as cleavage from the polymer residue. Thus, sulfonyl chlorides having polymer residues provide useful intermediates in combinatorial synthesis.

[0003] A conventional method for producing a sulfonyl chloride having a polymer residue has been developed by three steps of alkylation, hydrolysis and chlorination of merrifield resin with alkyllithium having a sulfonic acid ester. Method for synthesizing sulfonyl chloride having a group [Journal of the American Chemical Societ
y), 118, 9998 (1996)], a sulfonyl chloride having a polymer residue was obtained from Merrifield resin through O-alkylation with 4-hydroxybenzenesulfonic acid sodium salt and chlorination through two steps. Method of synthesis [Journal of Organic Chemistry, 62
Vol. 9326 (1997)] and a sulfonyl chloride having a polymer residue directly bonded to a benzene ring in a polystyrene resin commercially available from Argonaute Technologies, Inc. (polystyrene sulfonyl chloride).

[0004] A conventional method for producing an indanone derivative having a polymer residue is a method in which a hydroxyl group bonded to a sulfone derivative having an indanone skeleton via a spacer moiety is introduced into diethylhydrosilane having a polymer residue. (Japanese Patent Application No. 2000-76405). Indanone derivatives having this polymer residue can be used for various vitamin D
It is a very important intermediate for efficient synthesis of derivatives (Japanese Patent Application No. 2000-76405).

[0005]

SUMMARY OF THE INVENTION Sulfonyl chloride having a polymer residue is supported on a component of a physiologically active derivative, by modifying a substrate on the polymer residue, and by a nucleophilic substitution reaction of various nucleophiles. The method of synthesizing a physiologically active derivative by excision from a polymer residue is a method of separating and purifying the polymer residue after reaction on the polymer residue only by washing the polymer residue carrying the substrate. To simplify the synthesis of However, conventional syntheses of sulfonyl chlorides with polymer residues often require more than one step, which not only takes longer to synthesize, but also adds more uncertainties to the product. The conventional sulfonyl chloride having a polymer residue has no reactive site capable of being cleaved under mildly acidic conditions between the chlorosulfonyl group and the polymer residue,
Excision of a substrate on a polymer residue is only a nucleophilic substitution reaction with a sulfone derivative and a nucleophile capable of reacting with the sulfone derivative. In addition, conventional products often have difficulty reacting with very sterically bulky substrates due to the short distance between the chlorosulfonyl group and the polymer residue.

Accordingly, it is an object of the present invention to provide a method for synthesizing a sulfonyl chloride having a polymer residue from a polymer residue having a certain functional group in only one step in a short time. In addition, it has a polymer residue having a sufficient distance between the chlorosulfonyl group and the polymer residue, and having a functional group which can be cleaved under mildly acidic conditions in addition to the nucleophilic substitution reaction with the sulfone derivative. It is to provide a sulfonyl chloride.

In particular, an object of the present invention is to provide a method for more easily producing various indanone derivatives having a polymer residue by reacting the indanone derivative with a sulfonyl chloride having a polymer residue. is there.
In the conventional method for producing an indanone derivative having a polymer residue, the substrate before being supported on the polymer residue has a spacer containing a common sulfone derivative. Synthesis requires multiple steps. By inventing a polymer residue having a sulfonyl chloride that generates a sulfone derivative that is a common moiety, the synthesis of a substrate before being supported on the polymer residue is simplified, and as a result, various indanones having a polymer residue are obtained. This simplifies the method for producing the derivative and further simplifies the method for producing various vitamin D derivatives as the target compounds.

[0008]

According to the present invention, formula (A):

[0009]

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Wherein R ¹⁰⁰ is an alkyl group having an oxygen function, an alkenyl group having an oxygen function, an alkynyl group having an oxygen function, Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰¹ represents a polymer residue which may have a substituent, and R ¹⁰² and R ¹⁰³ each independently represent an alkyl group, an alkenyl group, an alkynyl group, an aryl group or There is provided a sulfone derivative represented by an aralkyl group (the above groups may have a substituent).

According to the present invention, the formula (B):

[0012]

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Wherein R ¹⁰⁰ is an alkyl group having an oxygen function, an alkenyl group having an oxygen function, an alkynyl group having an oxygen function, Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰⁴ represents a polystyrene chain which may have a substituent, and n is an integer of 0 to 2).

According to the present invention, there is further provided a compound of formula (C):

[0015]

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(Wherein, R ¹⁰⁵ represents a residue of a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, and m is an integer of 2 to 20) Is provided.

According to the present invention, further, formula (D):

[0018]

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[Wherein R ¹⁰⁰ represents an alkyl group having an oxygen functional group, an alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, or an oxygen functional group. Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰¹ represents a polymer residue which may have a substituent, and R ¹⁰² and R ¹⁰³ each independently represent an alkyl group, an alkenyl group, an alkynyl group, an aryl group or An aralkyl group (the above groups may have a substituent);
¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups are an oxygen atom,
(It may have a nitrogen atom, a sulfur atom, a halogen atom, and may have a substituent which may contain those atoms.)
Is represented.) Is provided.

According to the present invention, furthermore, the formula (E):

[0021]

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(Wherein R ¹⁰⁰ represents an alkyl group having an oxygen functional group, an alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, or an oxygen functional group. Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰⁴ represents a polystyrene chain which may have a substituent;
¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups are an oxygen atom,
(It may have a nitrogen atom, a sulfur atom, a halogen atom, and may have a substituent which may contain those atoms.)
Wherein n is an integer of 0 to 2).

According to the present invention, furthermore, formula (F):

[0024]

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(Wherein, R ¹⁰⁵ represents a polymer residue having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, and R ¹⁰⁶ represents an alkyl group, an alkenyl group, or an alkynyl group. , An aryl group or an aralkyl group (the above groups are
Which may have an oxygen atom, a nitrogen atom, a sulfur atom, or a halogen atom, or may have a substituent which may include those atoms), and m is an integer of 2 to 20). Are provided.

According to the present invention, there is further provided a polymer having a reactive functional group capable of bonding to a hydroxyl group and optionally having a substituent, and a compound represented by the formula (G):

[0027]

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(Wherein R ¹⁰⁰ ′ represents an alkyl group having a hydroxyl group, an alkenyl group having a hydroxyl group, an alkynyl group having a hydroxyl group, an aryl group having a hydroxyl group, or a hydroxyl group. Aralkyl groups (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, and may have a substituent which may contain those atoms)) Reacting the compound with a compound in the presence of an acid or a base to obtain a compound of the formula (H):

[0029]

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Wherein R ¹⁰⁰ is as defined above,
R ¹⁰⁵ has a reactive functional group capable of bonding to a hydroxyl group and represents a polymer residue which may have a substituent).

According to the invention, furthermore, the compounds of the formula (I):

[0032]

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[Wherein R¹⁰¹ May have a substituent
A polymer residue, R¹⁰² And R^{Ten Three} Is German
First, an alkyl group, an alkenyl group, an alkynyl group,
Or an aralkyl group (the above groups have a substituent
And Y is a group reactive with a hydroxyl group.
A hydrogen atom, a halogen atom, an alkylsulfonyl group,
Alkenylsulfonyl, alkynylsulfonyl, a
A reelsulfonyl group or an aralkylsulfonyl group
And a compound represented by the formula (G)
Is reacted in the presence of a base to give a compound of the formula (A):

[0034]

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There is provided a process for preparing a sulfone derivative of the formula wherein R ¹⁰⁰ and R ¹⁰¹ and R ¹⁰² and R ¹⁰³ are as defined above.

According to the present invention, further, a polymer having a vinyloxy moiety and optionally having a substituent is reacted with the compound of the formula (G) in the presence of an acid to obtain chloro. A method for producing a sulfone derivative having a sulfonyl group is provided.

According to the present invention, furthermore, the formula (J):

[0038]

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(Wherein R ¹⁰⁴ represents a polystyrene chain which may have a substituent, and n is an integer of 0 to 2), and a compound of the above formula (G), The reaction is carried out in the presence of the compound of formula (B):

[0040]

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A process is provided for preparing a sulfone derivative of the formula wherein R ¹⁰⁰ , R ¹⁰⁴ and n are as defined above.

According to the present invention, there is further provided a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, and a compound represented by the formula (K):

[0043]

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A compound of the formula (C) is reacted with a compound of the formula (C) wherein m is an integer of 2 to 20 in the presence of an acid or a base.

[0045]

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(Wherein, R ¹⁰⁵ represents a polymer residue having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, and m is an integer of 2 to 20) And a method for producing a sulfone derivative represented by the formula:

According to the invention, furthermore, the formula (L):

[0048]

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(Wherein R ¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, Which may have a substituent which may contain an atom of the formula (A):

[0050]

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(Wherein R ¹⁰⁰ represents an alkyl group having an oxygen function, an alkenyl group having an oxygen function, an alkynyl group having an oxygen function, Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰¹ represents a polymer residue which may have a substituent, and R ¹⁰² ,
And R ¹⁰³ are each independently a polymer represented by an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have a substituent); And reacting in the presence of

[0052]

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(Wherein R ¹⁰⁶ is an alkyl group, alkenyl group, alkynyl group, aryl group or aralkyl group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, R ¹⁰⁰ , R ¹⁰¹ , and R ^100
102 and R ¹⁰³ are as defined above).

According to the invention, furthermore, the formula (L):

[0055]

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(Wherein R ¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, A compound having the formula (B):

[0057]

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(Wherein R ¹⁰⁰ represents an alkyl group having an oxygen functional group, an alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰⁴ represents a polystyrene chain which may have a substituent, and n is an integer of 0 to 2) in the presence of a base,
And reacting with formula (E):

[0059]

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(Wherein R ¹⁰⁰ , R ¹⁰⁴ , R ¹⁰⁶ and n are as defined above).

According to the present invention, furthermore, the formula (L):

[0062]

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(Wherein R ¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, And a substituent which may contain an atom of the formula (C):

[0064]

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(Wherein, R ¹⁰⁵ represents a polymer residue having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, and m is an integer of 2 to 20) With a compound represented by the formula (F):

[0066]

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There is provided a process for producing a sulfone derivative represented by the formula: wherein R ¹⁰⁵ , R ¹⁰⁶ and m are as defined above.

According to the present invention, furthermore, formula (N):

[0069]

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(Wherein R ¹⁰⁷ , R ¹⁰⁸ and R ¹⁰⁹ each independently represent an alkyl group, alkenyl group, alkynyl group, aryl group, aralkyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy A group or an aralkyloxy group (the above groups may have a substituent), or a hydrogen atom or a hydroxyl group, or may have a substituent by two groups of R ¹⁰⁸ and R ¹⁰⁹ May form an acetal body,
These may be taken together to form an optionally substituted ylidene group, and X and Z are each independently
A hydrogen atom, a hydroxyl group or an ether group, an ester group or a silyloxy group derived from a hydroxyl group, or X and Z taken together represent an oxygen atom, a ketal group or an optionally protected cyanohydrin group) And a tetrahydroindane derivative of formula (H):

[0071]

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(Wherein R ¹⁰⁰ represents an alkyl group having an oxygen functional group, an alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, Aryl groups or aralkyl groups having an oxygen functional group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or have a substituent which may contain those atoms) R ¹⁰⁵ represents a polymer residue having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent), and a compound represented by the following formula: The reaction is carried out in the presence of the compound of formula (P):

[0073]

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(Where R ¹⁰⁰ , R ¹⁰⁵ , R ¹⁰⁷ , R
¹⁰⁸ , R ¹⁰⁹ , X and Z are as defined above).

[0075]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The "oxygen functional group" is a reactive residue between a reactive group and a hydroxyl group, and specifically includes oxygen.

The alkyl group represented by the substituent in the above general formula is preferably an alkyl group having 1 to 20 carbon atoms and may be linear or branched, for example, a methyl group, an ethyl group, n-propyl group, isopropyl group, n-
Butyl group, 1-methylpropyl group, 1-ethylethyl group, 2-methylpropyl group, n-pentyl group, 1-methylbutyl group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2- Dimethylpropyl group, 1-
Ethylpropyl group, n-hexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group,
4-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,2-dimethylbutyl group, 2, 3-dimethylbutyl group, 3,3-
Dimethylbutyl group, 1,1,2-trimethylpropyl group, 1,2,2-trimethylpropyl group, 1-ethyl-
1-methylpropyl group, 1-ethyl-2-methylpropyl group, n-heptyl group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 5-methylhexyl group , 1,1-dimethylpentyl group, 1,2-dimethylpentyl group, 1,3-dimethylpentyl group, 1,4-dimethylpentyl group, 2,2
-Dimethylpentyl group, 2,3-dimethylpentyl group,
2,4-dimethylpentyl group, 3,3-dimethylpentyl group, 3,4-dimethylpentyl group, 4,4-dimethylpentyl group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, 1,1,2-trimethylbutyl group, 1,1,3-trimethylbutyl group, 1,2,2
2-trimethylbutyl group, 1,2,3-trimethylbutyl group, 1,3,3-trimethylbutyl group, 2,2,3-
Trimethylbutyl group, 2,3,3-trimethylbutyl group, 1-ethyl-1-methylbutyl group, 1-ethyl-2
-Methylbutyl group, 1-ethyl-3-methylbutyl group,
2-ethyl-2-methylbutyl group, 2-ethyl-3-methylbutyl group, 1-n-propylbutyl group, 1- (1-
Methylethyl) butyl group, 1,1,2,2-tetramethylpropyl group, 1-ethyl-1,2-dimethylpropyl group, 1-ethyl-2,2-dimethylpropyl group, 1-
(1-methylethyl) -1-methylpropyl group, 1-
(1-methylethyl) -2-methylpropyl group, n-octyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5
-Methylheptyl group, 6-methylheptyl group, 1,1-
Dimethylhexyl group, 1,2-dimethylhexyl group,
1,3-dimethylhexyl group, 1,4-dimethylhexyl group, 1,5-dimethylhexyl group, 2,2-dimethylhexyl group, 2,3-dimethylhexyl group, 2,4-dimethylhexyl group, 2, 5-dimethylhexyl group, 3,
3-dimethylhexyl group, 3,4-dimethylhexyl group, 3,5-dimethylhexyl group, 4,4-dimethylhexyl group, 4,5-dimethylhexyl group, 5,5-dimethylhexyl group, 1,1, 2-trimethylpentyl group,
1,1,3-trimethylpentyl group, 1,1,4-trimethylpentyl group, 1,2,2-trimethylpentyl group, 1,2,3-trimethylpentyl group, 1,2,4-
Trimethylpentyl group, 2,2,3-trimethylpentyl group, 2,2,4-trimethylpentyl group, 3,3,4
-Trimethylpentyl group, 1-ethyl-1-methylpentyl group, 1-ethyl-2-methylpentyl group, 1-ethyl-3-methylpentyl group, 1-ethyl-4-methylpentyl group, 1-methyl-2 -Ethylpentyl group, 1-methyl-3-ethylpentyl group, 1- (n-propyl) pentyl group, 2- (n-propyl) pentyl group, 1- (1
-Methylethyl) pentyl group, 2- (1-methylethyl) pentyl group, 3- (1-methylethyl) pentyl group, 1,1,2,2-tetramethylbutyl group, 1,1,
2,3-tetramethylbutyl group, 1,1,3,3-tetramethylbutyl group, 1,2,2,3-tetramethylbutyl group, 1,2,3,3-tetramethylbutyl group, 2,
2,3,3-tetramethylbutyl group, 1-ethyl-1,
2-dimethylbutyl group, 1-ethyl-1,3-dimethylbutyl group, 1-ethyl-2,3-dimethylbutyl group, 1
-Ethyl-3,3-dimethylbutyl group, 1-methyl-1
-(N-propyl) butyl group, 2-methyl-1- (n-
Propyl) butyl group, 3-methyl-1- (n-propyl) butyl group, 1-methyl-1- (1-methylethyl)
Butyl group, 2-methyl-1- (1-methylethyl) butyl group, 3-methyl-1- (1-methylethyl) butyl group, 1- (1,1-dimethylethyl) butyl group, 2-
(1,1-dimethylethyl) butyl group, 1,2-dimethyl-1- (1-methylethyl) propyl group, 2,2-dimethyl-1- (1-methylethyl) propyl group, 1-ethyl-1 , 2,2-trimethylpropyl group.

The substituent which the alkyl group may have may be any substituent as long as the reaction is not hindered. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group,
Examples thereof include an alkylthio group, an alkenylthio group, an alkynylthio group, an arylthio group, and an aralkylthio group. These groups may form an acetal or thioacetal. The above-mentioned alkyl group includes those which may be substituted with a polymer residue which may have a substituent.

The alkenyl group represented by the substituent in the above formula is preferably an alkenyl group having 2 to 20 carbon atoms, which may be linear or branched, for example, a vinyl group or a 1-propene group. , 2-propene group, 1-methyl-
1-vinyl group, 1-butenyl group, 2-butenyl group, 3-
Butenyl group, 1-methyl-1-propenyl group, 2-methyl-1-propenyl group, 1-methyl-2-propenyl group, 2-methyl-2-propenyl group, 1-methylidene-
1-propane group, 1-pentenyl group, 1-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl-1-butenyl group, 1-methyl-2-butenyl group, 1-
Methyl-3-butenyl group, 1-methylidenebutyl group, 2
-Methyl-1-butenyl group, 2-methyl-2-butenyl group, 2-methyl-3-butenyl group, 2-methylidenebutyl group, 3-methyl-1-butenyl group, 3-methyl-2-
Butenyl group, 3-methyl-3-butenyl group, 1-ethyl-1-propenyl group, 1-ethyl-2-propenyl group,
1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group, 1-methyl-1-pentenyl group, 1-methyl-2-pentenyl group,
1-methyl-3-pentenyl group, 1-methyl-4-pentenyl group, 1-methylidenepentyl group, 2-methyl-1
-Pentenyl group, 2-methyl-2-pentenyl group, 2-
A methyl-3-pentenyl group, a 2-methyl-4-pentenyl group, a 2-methylidenepentyl group, a 3-methyl-1-pentenyl group, a 3-methyl-2-pentenyl group, a 3-methyl-3-pentenyl group, 3-methyl-4-pentenyl group, 3-methylidenepentyl group, 4-methyl-1-pentenyl group, 4-methyl-2-pentenyl group, 4-methyl-3-pentenyl group, 4-methyl-4-pentenyl Group,
1-ethyl-1-butenyl group, 1-ethyl-2-butenyl group, 1-ethyl-3-butenyl group, 2-ethyl-1-
Butenyl group, 2-ethyl-2-butenyl group, 2-ethyl-3-butenyl group, 1- (1-methylethyl) -1-propenyl group, 1- (1-methylethyl) -2-propenyl group, 1 -Ethyl-2-methyl-1-propenyl group, 1
-Ethyl-2-methyl-2-propenyl group, 1-heptenyl group, 2-heptenyl group, 3-heptenyl group, 4-heptenyl group, 5-heptenyl group, 7-heptenyl group, 1
-Methyl-1-hexenyl group, 1-methyl-2-hexenyl group, 1-methyl-3-hexenyl group, 1-methyl-
4-hexenyl group, 1-methyl-5-hexenyl group, 1
-Methylidenehexyl group, 2-methyl-1-hexenyl group, 2-methyl-2-hexenyl group, 2-methyl-3-
Hexenyl group, 2-methyl-4-hexenyl group, 2-methyl-5-hexenyl group, 2-methylidenehexyl group,
3-methyl-1-hexenyl group, 3-methyl-2-hexenyl group, 3-methyl-3-hexenyl group, 3-methyl-4-hexenyl group, 3-methyl-5-hexenyl group,
3-methylidenehexyl group, 4-methyl-1-hexenyl group, 4-methyl-2-hexenyl group, 4-methyl-3
-Hexenyl group, 4-methyl-4-hexenyl group, 4-
Methyl-5-hexenyl group, 4-methylidenehexyl group, 5-methyl-1-hexenyl group, 5-methyl-2-
Hexenyl group, 5-methyl-3-hexenyl group, 5-methyl-4-hexenyl group, 5-methyl-5-hexenyl group, 1-ethyl-1-pentenyl group, 1-ethyl-2-
Pentenyl group, 1-ethyl-3-pentenyl group, 1-ethyl-4-pentenyl group, 2-ethyl-1-pentenyl group, 2-ethyl-2-pentenyl group, 2-ethyl-3-
Pentenyl group, 2-ethyl-4-pentenyl group, 3-ethyl-1-pentenyl group, 3-ethyl-2-pentenyl group, 3-ethyl-3-pentenyl group, 3-ethyl-4-
Pentenyl group, 1,1-dimethyl-2-pentenyl group,
1,1-dimethyl-3-pentenyl group, 1,1-dimethyl-4-pentenyl group, 2,2-dimethyl-3-pentenyl group, 2,2-dimethyl-4-pentenyl group, 3,3
-Dimethyl-1-pentenyl group, 3,3-dimethyl-4
-Pentenyl group, 4,4-dimethyl-1-pentenyl group, 4,4-dimethyl-2-pentenyl group, 1,2-dimethyl-1-pentenyl group, 1,2-dimethyl-2-pentenyl group, 1, 2-dimethyl-3-pentenyl group,
1,2-dimethyl-4-pentenyl group, 1-methylidene-2-methylpentyl group, 2-methylidene-1-methylpentyl group, 1,3-dimethyl-1-pentenyl group,
1,3-dimethyl-2-pentenyl group, 1,3-dimethyl-3-pentenyl group, 1,3-dimethyl-4-pentenyl group, 1-methylidene-3-methylpentyl group, 3-
Methylidene-1-methylpentyl group, 1,4-dimethyl-1-pentenyl group, 1,4-dimethyl-2-pentenyl group, 1,4-dimethyl-3-pentenyl group, 1,4-
Dimethyl-4-pentenyl group, 1-methylidene-4-methylpentyl group, 1,1,2-trimethyl-2-butenyl group, 1,1,2-trimethyl-3-butenyl group, 1,
1-dimethyl-2-methylidenebutyl group, 1,1,3-
Trimethyl-2-butenyl group, 1,1,3-trimethyl-3-butenyl group, 1,2,2-trimethyl-3-butenyl group, 2,2-dimethyl-1-methylidenebutyl group,
1,2,3-trimethyl-1-butenyl group, 1,2,3
-Trimethyl-2-butenyl group, 1,2,3-trimethyl-3-butenyl group, 2,3-dimethyl-1-methylidenebutyl group, 1,3-dimethyl-2-methylidenebutyl group, 2,2,3-trimethyl -3-butenyl group, 2,
3,3-trimethyl-1-butenyl group, 3,3-dimethyl-2-methylidenebutyl group, 1-ethyl-1-methyl-2-butenyl group, 1-ethyl-1-methyl-3-butenyl group, 1- Ethynyl-1-methylbutyl group, 1-ethyl-2-methyl-1-butenyl group, 1-ethyl-2-methyl-2-butenyl group, 1-ethyl-2-methyl-3-
Butenyl group, 1-ethynyl-2-methylbutyl group, 1-
Ethylidene-2-methylbutyl group, 1-ethyl-3-methyl-1-butenyl group, 1-ethyl-3-methyl-2-
Butenyl group, 1-ethyl-3-methyl-3-butenyl group, 1-ethynyl-3-methylbutyl group, 1-ethylidene-3-methylbutyl group, 1-ethyl-3-methyl-1
-Butenyl group, 1-ethyl-3-methyl-2-butenyl group, 1-ethyl-3-methyl-3-butenyl group, 1-ethynyl-3-methylbutyl group, 1-ethylidene-3-methylbutyl group, 1- Methyl-2-ethyl-1-butenyl group, 1-methyl-2-ethyl-2-butenyl group, 1-methyl-2-ethyl-3-butenyl group, 2-methyl-2-
Ethyl-3-butenyl group, 1- (1-methylethyl)-
1-butenyl group, 1- (1-methylethyl) -2-butenyl group, 1- (1-methylethyl) -3-butenyl group,
1- (1-methylethylidene) butyl group, 1- (1-methyleneethyl) butyl group, 2- (1-methylethyl)-
1-butenyl group, 2- (1-methylethyl) -2-butenyl group, 2- (1-methylethyl) -3-butenyl group,
Examples thereof include a 2- (1-methylethylidene) butyl group and a 2- (1-methyleneethyl) butyl group.

The substituent which the alkenyl group may have may be any substituent as long as it does not hinder the reaction. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group ,
These groups may form an acetal form or a thioacetal form. The alkenyl group includes those which may be substituted with a polymer residue which may have a substituent.

The alkynyl group represented by the substituent in the above general formula is preferably an alkynyl group having 2 to 20 carbon atoms, which may be linear or branched, for example, an acetylene group and a 1-propyne group. A 2-propyne group, a 1-butyne group, a 2-butyne group, a 3-butyne group, a 1-pentyne group,
2-pentyne group, 3-pentyne group, 4-pentyne group, 3
-Methyl-1-propyne group, 2-ethenylpropane group,
1-hexyne group, 2-hexyne group, 3-hexyne group, 4
-Hexyne group, 5-hexyne group, 3-methyl-1-pentyne group, 4-methyl-1-pentyne group, 3,3-dimethyl-1-butyne group, 4-methyl-2-pentyne group, 2-
Methyl-3-pentyne group, 1,1-dimethyl-3-butyne group, 1,1-dimethyl-4-butyne group, 1,2-dimethyl-4-butyne group, 2,2-dimethyl-4-butyne group , 2-ethyl-3-butyne group, 3-ethyl-3-butyne group, 2,2-dimethyl-4-butyne group and the like.

The substituent which the alkynyl group may have may be any substituent as long as it does not hinder the reaction. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group ,
These groups may form an acetal form or a thioacetal form. The alkynyl group includes those which may be substituted with a polymer residue which may have a substituent.

The aryl group represented by the substituent in the above general formula is preferably an aryl group having 6 to 20 carbon atoms, such as a phenyl group, an o-methylphenyl group, an m-methylphenyl group and a p-methylphenyl group. And a naphthyl group.

The substituent which the aryl group may have may be any substituent as long as it does not hinder the reaction. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group,
Examples thereof include an alkylthio group, an alkenylthio group, an alkynylthio group, an arylthio group, and an aralkylthio group. These groups may form an acetal or thioacetal. The aryl group includes those which may be substituted with a polymer residue which may have a substituent.

The aralkyl group represented by the substituent in the above general formula is preferably an aralkyl group having 7 to 20 carbon atoms, for example, a benzyl group, an o-methylbenzyl group, an m-
Examples include a methylbenzyl group, a p-methylbenzyl group, and a naphthylmethylene group.

The substituent which the aralkyl group may have may be any substituent as long as it does not hinder the reaction. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group ,
These groups may form an acetal form or a thioacetal form. The aralkyl groups include those which may be substituted with a polymer residue which may have a substituent.

The alkyloxy group represented by the substituent in the above general formula includes, for example, a polymer residue which may have a substituent or an alkyl group which may be substituted by a substituent, And an alkyloxy group bonded thereto.

The substituent which the alkyloxy group may have may be any substituent as long as the reaction is not hindered. For example, a hydrogen atom, a fluorine atom,
Chlorine, bromine, iodine, nitrogen, sulfur, hydroxyl, alkyloxy, alkenyloxy,
Examples include an alkynyloxy group, an aryloxy group, an aralkyloxy group, an alkylthio group, an alkenylthio group, an alkynylthio group, an arylthio group, and an aralkylthio group, and these groups may form an acetal or thioacetal. . The alkyloxy group includes those which may be substituted with a polymer residue which may have a substituent.

Examples of the alkenyloxy group represented by the substituent in the above general formula include, for example, a polymer residue which may have a substituent or an alkenyl group which may be substituted with an oxygen atom. And an attached alkenyloxy group.

The substituent which the alkenyloxy group may have may be any substituent as long as the reaction is not hindered. For example, a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, Iodine atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group These groups may form an acetal form or a thioacetal form. The alkenyloxy group includes those which may be substituted with a polymer residue which may have a substituent.

Examples of the alkynyloxy group represented by the substituent in the above general formula include, for example, the above-mentioned polymer residue which may have a substituent or the above-mentioned alkynyl group which may be substituted by a substituent. And an alkynyloxy group bonded thereto.

The substituent which the alkynyloxy group may have may be any substituent as long as the reaction is not hindered. For example, a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, Iodine atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group These groups may form an acetal form or a thioacetal form. The alkynyloxy group includes those which may be substituted with a polymer residue which may have a substituent.

The aryloxy group represented by the substituent in the above general formula includes, for example, the above-mentioned polymer residue which may have a substituent or the above-mentioned aryl group which may be substituted by a substituent, And an aryloxy group bonded thereto.

The substituent which the aryloxy group may have may be any substituent as long as the reaction is not hindered. For example, a hydrogen atom, a fluorine atom,
Chlorine, bromine, iodine, nitrogen, sulfur, hydroxyl, alkyloxy, alkenyloxy,
Examples include an alkynyloxy group, an aryloxy group, an aralkyloxy group, an alkylthio group, an alkenylthio group, an alkynylthio group, an arylthio group, and an aralkylthio group, and these groups may form an acetal or thioacetal. . The aryloxy group includes those which may be substituted with a polymer residue which may have a substituent.

The aralkyloxy group represented by the substituent in the above general formula includes, for example, the above-mentioned polymer residue which may have a substituent or the above-mentioned aralkyl group which may have a substituent. And an aralkyloxy group bonded thereto.

The substituent which the aralkyloxy group may have may be any substituent as long as it does not hinder the reaction. For example, a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, Iodine atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group These groups may form an acetal form or a thioacetal form. The aralkyloxy group includes those optionally substituted with a polymer residue which may have a substituent.

In the acetal compound which may have a substituent in the above general formula, the carbon number of the alkyl moiety is each
Chain acetal having an alkyloxy group which is the same or different and may be linear or branched alkyl, such as dimethyl acetal, diethyl acetal, di-n-propyl acetal, diisopropyl acetal, ethyl methyl acetal, etc. Chain acetal;
A cyclic acetal in which the alkyl moiety of the alkyloxy moiety forming the ring is a linear or branched alkyl, such as ethylene acetal, propylene acetal, trimethylene acetal, 1-methyltrimethylene acetal, Methyltrimethylene acetal,
And cyclic acetal such as 1,1-dimethyltrimethylene acetal, 1,2-dimethyltrimethylene acetal, 1,3-dimethyltrimethylene acetal, and 2,2-dimethyltrimethylene acetal.

The substituent which the acetal compound may have may be any substituent as long as it does not hinder the reaction. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group, alkylthio group, alkenylthio group, alkynylthio group, arylthio group, aralkylthio group ,
These groups may form an acetal form or a thioacetal form. Further, the acetal form includes those which may be substituted with a polymer residue which may have a substituent.

The ylidene group which may have a substituent in the above general formula includes those having a double bond and those forming a ring structure. Those having a double bond may be linear or branched. For example, methylidene, ethylidene, propylidene, 1-methylethylidene, 1-methylpropylidene, 2-methylpropylidene, 1,1-dimethylpropylidene, 1,2-
Examples thereof include a dimethylpropylidene group, a 1,3-dimethylpropylidene group, and a 2,2-dimethylpropylidene group.

The substituent which the above-mentioned ylidene group may have may be any substituent as long as it does not hinder the reaction. Examples thereof include a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Atom, nitrogen atom, sulfur atom, hydroxyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group, aralkyloxy group,
Examples thereof include an alkylthio group, an alkenylthio group, an alkynylthio group, an arylthio group, and an aralkylthio group. These groups may form an acetal or thioacetal. The above-mentioned ylidene group includes those which may be substituted with a polymer residue which may have a substituent.

Among the groups represented by the substituents X and Z in the above formula, examples of the ether group include a methoxymethyloxy group, an ethoxyethyloxy group, a tetrahydropyranyloxy group, an allyloxy group and a benzyloxy group. Acetyloxy group as an ester group,
Examples include a pivaloyloxy group, a benzoyloxy group, a methoxycarbonyloxy group, and a chloroacetyloxy group. Examples of the silyloxy group include a trimethylsilyloxy group, a triethylsilyloxy group,
Examples thereof include a t-butyldimethylsilyloxy group, a triisopropyloxy group, and a diphenylmethylsilyloxy group. The ketal group which can be represented by X and Z together includes a dimethyl acetal group,
Diethyl acetal group, dibenzyl acetal group, 1,
Examples include a 3-dioxolane group, a 1,3-dioxane group, and the like. Examples of a protective group of the optionally protected cyanohydrin include a methoxymethyl group, an ethoxyethyl group, a tert-butyldimethylsilyl group, an acetyl group,
Examples include a benzoyl group.

Examples of the polymer of the polymer residue which may have a substituent contained in the substituents in the above general formula include ethylene, propylene, styrene, styrene derivatives (for example, α-methylstyrene), Methacrylates (eg, methyl methacrylate), acrylates (eg, acrylates), acrylonitrile, vinyl esters (eg, vinyl acetate), vinyl ethers (eg, methyl vinyl ether), butadiene, isoprene, isobutene, ethylene glycol, propylene glycol, ethylene oxide And various polymers of polymerizable monomers such as propylene oxide (homopolymers, random copolymers composed of two or more monomers, block polymers, graft polymers, etc.).

If the reaction is not hindered, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4 -Butanediol, 1,4-butenediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 1,3- Hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 1,9-nonanediol, catechol,
Polyesters of polyols such as 1,4-dibenzenemethanol and polycarboxylic acids such as malonic acid, succinic acid, glutaric acid, adipic acid and terephthalic acid (alternate copolymerization, from two or more kinds of polyols or polycarboxylic acids) Random block copolymers, block polymers, etc.).

Further, instead of the above polyol, ethylenediamine, 1,2-propanediamine, 1,3-propanediamine, 1,2-butanediamine, 1,3-butanediamine, 1,6 Polyamides of polyamines such as hexamethylenediamine, 1,9-nonanediamine, diaminobenzene and the above-mentioned polycarboxylic acids (polycondensation, random block copolymers comprising two or more polyamines or polycarboxylic acids, block polymers, etc.); No.

Preferred polymers include various polymers of ethylene, propylene, styrene and styrene derivatives.

In the present invention, the polymer residue which may have a substituent and the substituent of the polystyrene chain which may have a substituent may be any substituent as long as the reaction is not hindered. Although it may be, for example, a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a nitrogen atom, a sulfur atom, a hydroxyl group, an alkyloxy group, an alkenyloxy group, an alkynyloxy group, an aryloxy group, an aralkyloxy group, Examples thereof include an alkylthio group, an alkenylthio group, an alkynylthio group, an arylthio group, and an aralkylthio group. These groups may form an acetal or thioacetal.

These alkyloxy groups and alkenyloxy
Si group, alkynyloxy group, aryloxy group, aral
Killoxy, alkylthio, alkenylthio, a
Rukinylthio, arylthio, aralkylthio,
Alkyl moiety for acetal and thioacetal
Minute, alkenyl moiety, alkynyl moiety, aryl moiety,
Aralkyl part, acetal part, what kind of alk
Alkenyl, alkynyl, aryl, ara
Although it may be a alkyl group, for example, R^{Ten 0} Etc.
Alkyl, alkenyl, alkynyl, ant
And an aralkyl group and an acetal form.

These substituents may include a ring structure. Examples of such a ring structure include a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a cycloheptane ring and a cyclooctane ring. Saturated cycloalkane ring; cyclobutene ring, cyclopentene ring, cyclohexene ring, cycloheptene ring, cycloalkene ring such as cyclooctene ring; aryl group such as phenyl group; aralkyl group such as benzyl group; May be substituted with the above-mentioned substituents. Examples of the substituent include the alkyl group, alkenyl group, alkynyl group, aryl group, aralkyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, and aryloxy group described above. Groups, aralkyloxy groups, It may form an acetal body by these groups.

In the present invention, the molecular weight of the polymer residue in the polymer residue which may have a substituent is usually in the range of 500 to 5,000,000 in number average molecular weight, preferably in the range of 500 to 1,000,000. It is. The molecular weight of the polystyrene chain which may have a substituent is 500 to
About 5,000,000, preferably 500 to 100
0000.

In the present invention, a polymer residue which may have a substituent is defined as one or more reactive functional groups present at the terminal or side chain of the polymer, and as a result, Refers to the remaining groups. The functional group may be a functional group capable of forming any bonding mode as long as an organic compound such as an indane derivative can be chemically bonded to a polymer, and the bonding mode may be, for example, a carbon-carbon single layer. Bond, a carbon-carbon double bond, a carbon-carbon triple bond, an ether bond, a thioether bond, a silyloxy bond, an ester bond, an amide bond, a sulfonyloxy bond, and the like, and two or more of these bonds may be combined. Examples of the functional group include an ether group, a thioether group, a silyloxy group, an oxycarbonyl group, a dioxycarbonyl group, an amide group, and a sulfonyloxy group.

When the bond formed by the above polymer residue and an organic compound such as an indane derivative is a silyloxy bond, the substituent on the silicon atom constituting the silyloxy bond may be an alkyl group, an alkenyl group, an alkynyl group. group, an aryl group, may be substituted with an aralkyl group, an alkyl group as the substituent on these silyl group, an alkenyl group, an alkynyl group, an aryl group, the aralkyl group, for example an alkyl group represented by R ^100, alkenyl Groups, alkynyl groups, aryl groups and aralkyl groups.

Examples of the polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent include:
For example, halogen such as fluorine, chlorine, bromine and iodine; dialkylsilyl chloride, dialkylsilyl bromide, dialkylsilyl iodide, dialkenylsilyl chloride, dialkenylsilyl bromide, dialkenylsilyl iodide, dialkynylsilyl chloride, dialkynysilyl Bromide, dialkynylsilyl iodide, diaryl chloride, diaryl bromide, diaryl iodide, diaralkyl chloride,
Halogenosilyl groups such as dialkyl bromide and diaralkyl iodide; hydrosilyl groups such as dialkylsilyl hydride, dialkenylsilyl hydride, dialkynylsilyl hydride, diarylsilyl hydride, and diaralkyl silyl hydride; alkylsulfonyl silyl group and alkenyl sulfonirosilyl A sulfonyl silyl group such as a group, an alkynyl sulfonyl silyl group, an aryl sulfonyl silyl group, an aralkyl sulfonyl silyl group; an alkyl sulfonyl group, an alkenyl sulfonyl group, an alkynyl sulfonyl group, an aryl sulfonyl group, an aralkyl sulfonyl group, a carboxyl group, and an amide group. Having a vinyl ether such as a tetrahydropyranyl group, a dihydrofuranyl group or an ethoxyvinyl group which may have a substituent. Polymers. Such a halogenosilyl group, a hydrosilyl group, a sulfonylosyl group,
The alkyl, alkenyl, alkynyl, aryl, and aralkyl groups of the alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, arylsulfonyl, and aralkylsulfonyl groups are, for example, R
Examples thereof include an alkyl group, an alkenyl group, an alkynyl group, an aryl group, and an aralkyl group, such as ¹⁰⁰ , and these groups may have a substituent.

The indane derivatives represented by the general formulas (N) and (P) have geometric isomers, and in the present invention, all of them are also included.

Examples of the halogen atom for Y include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

[0114] alkylsulfonyl group in Y, alkenylsulfonyl groups, alkynylsulfonyl group, an arylsulfonyl group, the aralkyl sulfonyl group, e.g., alkyl group represented by ¹⁰⁰ like R of the above described alkenyl group, an alkynyl group, an aryl group, an aralkyl And a sulfonyl group composed of a group.

The functional group possessed by R ¹⁰⁰ and R ¹⁰⁶ may be a functional group capable of any binding mode as long as the reaction is not hindered.
A carbon single bond, a carbon-carbon double bond, a carbon-carbon triple bond, an ether bond, a thioether bond, a silyloxy bond, an ester bond, an amide bond, a peptide bond with various amino acids, a sulfonyloxy bond, and the like.
Two or more of these bonds may be combined, and as the functional group, an ether group, a thioether group, a silyloxy group, an oxycarbonyl group, a dioxycarbonyl group,
Examples include an amide group, a peptide group, and a sulfonyloxy group.

Sulfonyl chloride having a polymer residue (A), (B), (C), (H), a polymer having a vinyloxy moiety and optionally having a substituent and the above-mentioned formula (G) A method for producing a sulfonyl chloride produced by reacting the compound of the formula (1) with an acid is described below.

The sulfonyl chlorides (A), (C) and (H) having a polymer residue can be produced by any method, for example, each having a reactive functional group capable of binding to a hydroxyl group and having a substituent. A polymer which may have a group and a sulfonyl chloride having a hydroxyl group (G); a polymer having a silyl group (I) and a sulfonyl chloride having a hydroxyl group (G); and a functional group having a reactivity capable of binding to a hydroxyl group. A method of reacting a polymer having a substituent and a sulfonyl chloride (K) having a hydroxyl group in the presence of a base will be described.

As the base, any base can be used as long as the reaction proceeds and does not adversely affect the chlorosulfonyl group. For example, methyl lithium, ethyl lithium, n-propyl lithium, isopropyl lithium,
alkyl lithium such as n-butyl lithium; aryl lithium such as phenyl lithium; lithium amide, sodium amide, potassium amide, lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium dicyclohexylamide, sodium dicyclohexylamide, potassium dicyclohexylamide, lithium Metal amides such as bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide; metal hydrides such as lithium hydride, sodium hydride, potassium hydride; lithium methoxide, lithium ethoxide, lithium n-propyl oxide, lithium iso-propyl oxide, lithium n-butoxide, lithium 2 Butoxide, lithium tert- butoxide, sodium methoxide, sodium ethoxide, sodium n- propyl oxide, sodium is
o-propyl oxide, sodium n-butoxide, sodium 2-butoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium n-propyl oxide, potassium iso-propyl oxide, potassium n-butoxide, potassium 2-butoxide, Metal alkoxides such as potassium tert-butoxide; triethylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N, N
-Diethylaniline, N, N-dimethylaniline, 1.
Amine compounds such as 8-diazabicyclo [5.4.0] undecene;

The amount of the base to be used is preferably 1 molar equivalent or more, more preferably 1 to 10 molar equivalents, relative to the sulfonyl chloride (G) or (K) having a hydroxyl group.

The amount of the polymer (I) having a functional group having a reactivity capable of binding to a hydroxyl group and optionally having a substituent or the polymer (I) having a silyl group is determined based on the amount of the sulfonyl chloride (G ) Or (K), 0.0
It is preferably at least 01 molar equivalent, more preferably in the range of 0.01 to 10 molar equivalents.

The reaction is usually performed in a solvent that does not adversely influence the reaction. Examples of the solvent include ether solvents such as tetrahydrofuran, diethyl ether and dimethoxyethane; toluene, pentane, hexane, heptane,
Hydrocarbon solvents such as octane and petroleum ether; halogen-containing hydrocarbon solvents such as methylene chloride, dichloroethane, chlorobenzene and o-dichlorobenzene; amide solvents such as dimethylformamide and dimethylacetamide; alcohols such as methanol, ethanol and isopropanol System solvent; water or a mixed solvent thereof is used. The amount of the solvent to be used is generally preferably 1 to 200 times the weight of the sulfonyl chloride (G) or (K) having a hydroxyl group.

The reaction is usually carried out under an inert gas atmosphere to give a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent or a polymer (I) having a silyl group, A solution obtained by mixing a base or a base dissolved in the solvent with a sulfonyl chloride (G) or (K) having a hydroxyl group is added to the solvent, or a base or a base dissolved in the solvent and a sulfonyl chloride having a hydroxyl group are added to the solvent. A polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent or a polymer having a silyl group (I) is added to a solution obtained by mixing (G) or (K). It is done by doing.

The reaction temperature is preferably in the range not exceeding -100 ° C to 200 ° C, more preferably in the range of -40 ° C to 200 ° C.

Sulfonyl chloride having a hydroxyl group (G)
Alternatively, the production method of (K) may be any method,
For example, methyl 4-hydroxybenzenesulfonate and 9
-Mitsunobu reaction with tetrahydropyranyloxynonanol, followed by hydrolysis of the sulfonic ester, chlorination, deprotection of the tetrahydropyranyl group.

The sulfonyl chloride (A) or (C) or (H) having a polymer residue thus obtained is obtained.
Can be obtained by washing and filtering with an organic solvent such as diethyl ether, ethyl acetate, methylene chloride or the like to obtain an unreacted hydroxyl group-containing sulfonyl chloride (G) or (K).
Can be recovered in an organic solvent and, at the same time, can be obtained by filtration. Further, the basic substance can be removed by washing the sulfonyl chloride (A), (C) or (H) having a polymer residue obtained as a separated product with dilute hydrochloric acid or aqueous ammonium chloride. After that, it can be washed and dried with an organic solvent such as tetrahydrofuran, dimethylformamide, diethyl ether, ethyl acetate, methylene chloride, methanol, or a mixture of any organic solvent and water.

A sulfonyl chloride having a polymer residue (B), (C), (H), a polymer having a vinyloxy moiety and optionally having a substituent and a compound of the above formula (G) Any method can be used for producing the sulfonyl chloride produced by reacting in the presence of an acid. For example, each of the sulfonyl chlorides may have a reactive functional group capable of binding to a hydroxyl group and may have a substituent. The compound may have a sulfonyl chloride having a hydroxyl group (G), a polymer residue which may have a substituent having a vinyloxy moiety and a sulfonyl chloride having a hydroxyl group (G), and may have a substituent having a cyclic vinyloxy moiety. Sulfonyl chloride (G) having a polymer residue (J) and a hydroxyl group, a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent and having a hydroxyl group Ruhonirukurorido a method of reacting in the presence of acid (K) will be described.

As the acid, any acid may be used as long as it does not impair the chlorosulfonyl group. For example, hydrogen halides such as hydrogen fluoride, hydrogen chloride, hydrogen bromide and hydrogen iodide; sulfonic acids such as (+)-10-camphorsulfonic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid; Sulfuric acid; sulfates such as monosodium sulfate; sulfonium salts such as pyridinium p-toluenesulfonic acid; phosphoric acid; phosphates such as monosodium phosphate; perhydrohalic acids such as perchloric acid; Hydrohalic acid such as hypochlorous acid; acidic ion exchange resin; solid acid such as K-10 clay; organic acid such as trifluoroacetic acid; aluminum oxide, aluminum chloride, aluminum phosphate , Copper chloride, copper bromide, Lewis acids such as trimethylsilyl iodide; 2,3-dichloro-5,6-dicyano-
Examples include 1,4-benzoquinone and ceric ammonium nitrate.

The amount of the acid used is preferably 0.0001 molar equivalent or more, more preferably 0.001 to 10 molar equivalents, relative to the sulfonyl chloride (G) or (K) having a hydroxyl group.

A polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, a polymer residue having a vinyloxy moiety and a cyclic vinyloxy moiety is preferred. The amount of the polymer residue (J) which may have a substituent is 0.000 to the sulfonyl chloride (G) or (K) having a hydroxyl group.
One molar equivalent or more is preferable, and a range of 0.01 to 10 molar equivalents is more preferable.

The reaction is usually performed in a solvent that does not adversely influence the reaction. Examples of the solvent include ether solvents such as tetrahydrofuran, diethyl ether and dimethoxyethane; toluene, pentane, hexane, heptane,
Hydrocarbon solvents such as octane and petroleum ether; halogen-containing hydrocarbon solvents such as methylene chloride, dichloroethane, chlorobenzene and o-dichlorobenzene; amide solvents such as dimethylformamide and dimethylacetamide; alcohols such as methanol, ethanol and isopropanol System solvent; water or a mixed solvent thereof is used. The amount of the solvent to be used is generally preferably 1 to 200 times the weight of the sulfonyl chloride (G) or (K) having a hydroxyl group.

The reaction is generally carried out under an inert gas atmosphere, with a polymer having a reactive functional group capable of bonding to a hydroxyl group and optionally having a substituent or a polymer having a vinyloxy moiety. A good polymer residue or a polymer residue (J) which may have a substituent having a cyclic vinyloxy moiety is added to an acid in the above solvent or an acid dissolved in the above solvent and a sulfonyl chloride (G) having a hydroxyl group or ( K) is added to a mixed solution, or a solution obtained by mixing an acid in the solvent or an acid dissolved in the solvent with a sulfonyl chloride (G) or (K) having a hydroxyl group has a reactivity capable of binding to a hydroxyl group. A polymer having a functional group and optionally having a substituent or a polymer residue having a vinyloxy moiety or a substituent having a cyclic vinyloxy moiety; Performed by also adding or polymer residues (J) which was.

The reaction temperature is preferably in the range not exceeding -100 ° C to 200 ° C, more preferably in the range of -40 ° C to 200 ° C.

The thus obtained sulfonyl chloride having a polymer residue (B), (C) or (H) or a polymer having a vinyloxy moiety and optionally having a substituent, and the above formula The sulfonyl chloride produced by reacting the compound of (G) with an acid in the presence of an acid is washed and filtered with an organic solvent such as diethyl ether, ethyl acetate, methylene chloride or the like to obtain a sulfonyl chloride having an unreacted hydroxyl group. Chloride (G) or (K) can be recovered in an organic solvent and can be obtained by filtration at the same time.
Further, a sulfonyl chloride having a polymer residue (B), (C), (H) having a polymer residue obtained as a filtered product, or a polymer having a vinyloxy moiety and optionally having a substituent, and the above-mentioned formula (G) ) With a compound of the formula (1), in the presence of an acid, sulfonyl chloride, triethylamine,
The acidic substance can be removed by washing with an amine compound such as diisopropylethylamine or pyridine or a mixture thereof with an organic solvent, or an aqueous solution of an inorganic base such as sodium bicarbonate powder or a mixture thereof with an organic solvent. Then, tetrahydrofuran, dimethylformamide, diethyl ether, ethyl acetate, methylene chloride,
It can be washed and dried with an organic solvent such as methanol, or a mixture with any organic solvent or water.

The method for producing the sulfone derivatives (D), (E), (F) and (P) having a polymer residue will be described below.

The sulfone derivatives (D), (E), (F) and (P) having a polymer residue may be produced by any method, for example, a compound (L) having a hydroxyl group and a polymer residue. (A), a compound (L) having a hydroxyl group and a sulfonyl chloride (B) having a polymer residue, a compound (L) having a hydroxyl group and a sulfonyl chloride (C) having a polymer residue, and a hydroxyl group. A method for reacting an indane derivative (N) having the same with a sulfonyl chloride (H) having a polymer residue in the presence of a base will be described.

Any base can be used as long as the reaction proceeds and does not adversely affect the compound (L) having a hydroxyl group or the indane derivative (N) having a hydroxyl group, or the lack of a supported substrate from a polymer residue. May be. For example, alkyl lithium such as methyl lithium, ethyl lithium, n-propyl lithium, isopropyl lithium, n-butyl lithium; aryl lithium such as phenyl lithium; lithium amide, sodium amide, potassium amide, lithium diisopropylamide, sodium diisopropylamide, potassium Metal amides such as diisopropylamide, lithium dicyclohexylamide, sodium dicyclohexylamide, potassium dicyclohexylamide, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide; lithium hydride, sodium hydride, hydrogenation Metal hydrides such as potassium; lithium methoxide, lithium ethoxide, lithium n- Ropiruokishido, lithium iso-
Propyl oxide, lithium n-butoxide, lithium 2-butoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium n-propyl oxide, sodium iso-propyl oxide, sodium n-butoxide, sodium 2-butoxide, sodium tert Metal alkoxides such as butoxide, potassium methoxide, potassium ethoxide, potassium n-propyl oxide, potassium iso-propyl oxide, potassium n-butoxide, potassium 2-butoxide, potassium tert-butoxide; triethylamine, diisopropylethylamine, pyridine, -Dimethylaminopyridine, N, N-diethylaniline, N, N-dimethylaniline, 1.8-diazabicyclo [5.4.0] And amine compounds such as undecene and the like.

The amount of the base used is determined based on the sulfonyl chloride (A), (B), (C) or (H) having a polymer residue.
Is preferably at least 1 molar equivalent, more preferably 1 to 10 molar equivalents.

The amount of the sulfonyl chloride (A), (B), (C) or (H) having a polymer residue is based on the amount of the organic substance (L) having a hydroxyl group or the indane derivative (N) having a hydroxyl group. 0.001 molar equivalent or more is preferable, and the range of 0.01 to 10 molar equivalent is more preferable.

The reaction is usually performed in a solvent that does not adversely influence the reaction. Examples of the solvent include ether solvents such as tetrahydrofuran, diethyl ether and dimethoxyethane; toluene, pentane, hexane, heptane,
Hydrocarbon solvents such as octane and petroleum ether; halogen-containing hydrocarbon solvents such as methylene chloride, dichloroethane, chlorobenzene and o-dichlorobenzene; amide solvents such as dimethylformamide and dimethylacetamide; alcohols such as methanol, ethanol and isopropanol System solvent; water or a mixed solvent thereof is used. The amount of the solvent to be used is generally preferably 1 to 200 times the weight of the compound (L) having a hydroxyl group or the indane derivative (N) having a hydroxyl group.

The reaction is usually carried out under an inert gas atmosphere under the conditions of sulfonyl chlorides (A), (B),
To (C) or (H), a solution in which a base in the above solvent or a base dissolved in the above solvent and a compound having a hydroxyl group (L) or an indane derivative having a hydroxyl group (N) is added, or the base is added to the solvent. Alternatively, a sulfonyl chloride having a polymer residue (A), (B), or a solution obtained by mixing a base dissolved in the solvent and a compound having a hydroxyl group (L) or an indane derivative having a hydroxyl group (N) is mixed.
This is performed by adding (C) or (H).

The reaction temperature is preferably in a range not exceeding -100 ° C to 200 ° C, more preferably in a range of -40 ° C to 200 ° C.

The method for producing the indane derivative (N) having a hydroxyl group may be any method.
T .; Hijikuro, I .; Takahashi, TJ Am. Chem. Soc.
[1R- [1α (S
*), 3aβ, 7aα]]-octahydro-1- [2-
[(1,1-dimethylethyl) dimethylsilyloxy]
-1-methylethyl] -7a-methyl-4H-inden-4-one, or the literature Posner, GH; Lee, JK;
White, MC; Hutchings, RH; Dai, H .; Kachinsk
i, JL; Dolan, P .; Kensler, TWJ Org. Chem.
1997, 62, 3299. (S) -2-[(1
R, 3aR, 4S, 7aR) -Octahydro-4-
[(1,1-dimethylethyl) dimethylsilyloxy]
[7a-methyl-1H-inden-1-yl] propanal as a starting material by the method described in this patent or a method analogous thereto.

The sulfone derivative (D), (E), (F) or (P) having a polymer residue thus obtained is obtained.
For example, the unreacted compound (L) having a hydroxyl group or the indane derivative (N) having a hydroxyl group can be recovered in an organic solvent by washing and filtering with an organic solvent such as diethyl ether, ethyl acetate, and methylene chloride. It can be obtained by filtration at the same time as possible. Further, a sulfone derivative (D) having a polymer residue obtained as a filtered product,
The basic substance can be removed by washing (E), (F) or (P) with diluted hydrochloric acid and aqueous ammonium chloride. After that, it can be washed and dried with an organic solvent such as tetrahydrofuran, dimethylformamide, diethyl ether, ethyl acetate, methylene chloride, methanol, or a mixture of any organic solvent and water.

[0144]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the scope of the present invention is not limited to these Examples.

Example 1 Synthesis of methyl 4- (9-tetrahydropyranyloxynonane-1-oxy) benzenesulfonate 9-tetrahydropyranyloxy-1-nonanol (1.65 g, 6.14 mmol), methyl 4-hydroxy Benzenesulfonate (1.39 g, 7.37 mmol
l), triphenylphosphine (1.93 g, 7.37 m)
mol) and triethylamine (1.03 mL, 7.37 m)
mol) in dry tetrahydrofuran (50 mL) solution,
Diethyl azodicarboxylate (40% toluene solution, 3.21 mL, 7.37 mmol) at 0 ° C. under an argon atmosphere
Was added dropwise. After the reaction solution was stirred at the same temperature for 30 minutes, a few drops of water were added. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography with 10% ethyl acetate-hexane to give methyl 4- (9-tetrahydropyranyloxynonan-1-ane as a colorless liquid.
Oxy) benzenesulfonate (2.08 g, yield 82)
%).

¹ H NMR (270 MHz, CDCl ₃ ) δ 7.81 (d, J
= 8.9 Hz, 2H), 6.98 (d, J = 8.9 Hz, 2H), 4.56 (m, 1
H), 4.01 (t, J = 6.6 Hz, 2H), 3.86 (m, 1H), 3.74
(m, 1H), 3.71 (s, 3H), 3.48 (m, 1H), 3.37 (dt, J =
6.6, 9.6 Hz, 1H), 1.3-1.9 (m, 20H); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 163.5, 130.3, 126.2,
114.9, 98.9, 68.6, 67.7, 62.5, 56.0, 30.8, 29.8, 2
9.5, 29.4, 29.3, 29.0, 26.2, 25.9, 25.5, 19.8; IR (neat) 2870, 1579, 1483, 1452, 1351, 1251, 116
0, 992, 762, 580 cm ^-1 ; HRMS (ESI-TOF) (C ₂₁ H ₃₄ O ₆ Sna), calculated 437.1974 (M + N
a), Found 437.1961

[0147] Example 2 4- (9-tetrahydropyranyloxy nonane-1-oxy) benzene sulfonyl Rukurorido Synthesis of methyl 4- (9-tetrahydropyranyloxy nonane-1-oxy) benzene sulfonate (20.25 g,
To a solution of (48.85 mmol) in acetone (280 mL) at room temperature was added lithium chloride (4.14 g, 97.7 mmol). After stirring the reaction solution at 55 ° C. for 1.5 hours, the formed white precipitate was collected by filtration. The filtrate was concentrated and diluted with ether to obtain a precipitate again, which was collected by filtration. Both precipitates were dried in vacuo and the crude lithium 4- (9-tetrahydropyranyloxynonan-1-oxy) benzenesulfonate (2
1.0 g) as a white solid. Crude lithium 4
To a solution of-(9-tetrahydropyranyloxynonan-1-oxy) benzenesulfonate (21.0 g) in dimethylformamide (280 mL) at 0 ° C was added phosphorus pentachloride (15.3 g, 73.3 mmol). After the reaction solution was stirred at room temperature for 15 minutes, ice water was added. The mixture was extracted with ether, washed with saturated saline,
It was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with 7% ethyl acetate-hexane to give 4- (9
-Tetrahydropyranyloxynonane-1-oxy) benzenesulfonyl chloride (6.43 g, 31% yield)
I got In this purification, 4- (9-hydroxynonane-1-oxy) benzenesulfonyl chloride (5.35 g, 31% yield) was obtained as a white solid with 33% ethyl acetate-hexane, and this was dried with methylene chloride. Solvent (50
In the presence of 0.01 equivalents of (+)-10-camphorsulfonic acid (37 mg) in 1.1 mL), 1.1 equivalents of dihydropyran (1.6 mL, 18 mmol) were stirred at room temperature for 30 minutes to give 4 Converted to-(9-tetrahydropyranyloxynonane-1-oxy) benzenesulfonyl chloride (6.57 g, 98% yield).

Mp 46-48 ° C;¹ H NMR (270 MHz, CDCl_Three) δ 7.95 (d, J = 8.9 Hz, 2
H), 7.02 (d, J = 8.9Hz, 2H), 4.57 (m, 1H), 4.05
(t, J = 6.6 Hz, 2H), 3.87 (m, 1H), 3.74 (dt, J = 6.
8, 9.6 Hz, 1H), 3.49 (m, 1H), 3.38 (dt, J = 6.6,
9.6 Hz, 1H), 1.3-1.9 (m, 20H);¹³ C NMR (67.8 MHz, CDCl_Three) δ 164.6, 135.9, 129.6,
115.1, 99.0, 69.0, 67.7, 62.5, 30.9, 29.8, 29.5, 2
9.4, 29.3, 28.9, 26.3, 25.9, 25.6, 19.8; IR (KBr) 2
874, 1703, 1573, 1480, 1455, 1362, 1259, 1159, 102
0,574 cm^{- 1}; HRMS (ESI-TOF) (C₂₀H₃₂ClO_FiveS), 419.1659 (M +
H), found 419.1651

Example 3 4- (9-Hydroxynonane-1-oxy) benzenes
Synthesis of rufonyl chloride 4- (9-tetrahydropyranyloxynonan-1-oxy) benzenesulfonyl chloride (1.00 g, 2.
(+)-10-Camphorsulfonic acid (0.16 g, 0.69 mmol) was added to a solution of 30 mmol) in ethanol (12 mL) and tetrahydrofuran (5 mL) at room temperature, and the mixture was stirred for 2 hours. After adding saturated aqueous sodium bicarbonate at 0 ° C., the aqueous layer was extracted with ether, and the extract was washed with saturated saline and dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography with 15% ethyl acetate-hexane to give a colorless liquid.
-(9-Hydroxynonane-1-oxy) benzenesulfonyl chloride (652 mg, 81%).

¹ H NMR (270 MHz, CDCl ₃ ) δ 7.95 (d, J
= 8.9 Hz, 2H), 7.02 (d, J = 8.9Hz, 2H), 4.05 (t, J
= 6.6 Hz, 2H), 3.63 (t, J = 6.6 Hz, 2H), 1.81 (m,
2H), 1.3-1.8 (m, 12H); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 164.6, 135.8, 129.6,
115.1, 69.0, 63.0, 32.8, 29.5, 29.4, 29.2, 28.9, 2
5.9, 25.8; IR (neat) 3352, 2931, 1592, 1577, 1495, 1375, 126
8, 1168, 1085, 834, 789, 575 cm ^-1 ; HRMS (ESI-TOF) (C ₁₅ H ₂₃ ClO ₄ Sna), calculated 357.0903 (M
+ Na), found 357.0886

Example 4 4- [9-[(4-polystyrylbutyl) diethylsilyloxy] nonane-1 -oxy] benzenesulfonylc
Synthesis of chloride (4-polystyrylbutyl) diethylsilyl hydride (400 m
g, 0.296 mmol in terms of reactive site, into a 5 mL cylinder reactor at room temperature with 3 equivalents of 1,3-dichloro-5,5-dimethylhydantoin (175 mg, 0.88
(8 mmol) in dry methylene chloride (3 mL) was added.
After shaking for 1 hour, the reaction solution was filtered, and the resin was washed with dry methylene chloride (3 mL × 3) under an argon atmosphere. Immediately, 4- (9-hydroxynonane-1-oxy) benzenesulfonyl chloride (312 mg, 0.888 mmol) and diisopropylethylamine (0.31 mL, 1.8 mm)
ol) in dry methylene chloride (2.7 mL) was added and shaken at room temperature for 2 hours. The reaction solution was filtered, and the resin was washed with methylene chloride (3 mL × 2) to recover unreacted 4- (9-hydroxynonane-1-oxy) benzenesulfonyl chloride. In addition, the resin is tetrahydrofuran:
The mixture was washed twice with a water = 3: 1 solution (3 mL), methanol (3 mL), and a tetrahydrofuran: water = 3: 1 solution (3 mL), methanol (3 mL), and ether (3 mL). The obtained resin was dried under vacuum for 12 hours, and 4- [9-[(4-polystyrylbutyl) diethylsilyloxy] nonane-1-oxy] benzenesulfonyl chloride (486.6 mg, conversion to silyl hydride having the following physical properties) was obtained. (83% yield).

¹³ C SR-MAS NMR (400 MHz, CDCl ₃ ) δ 16
4.5, 136.0, 129.6, 115.2, 69.0, 63.0 FT-IR (resin) 2934, 1594, 1491, 1451, 1381, 1263,
1166, 1082, 1013, 832 cm ^-1

Example 5 (S) -2-[(1R, 3aR, 7aR) -octahydro-7a-methyl-4-oxo-4H-indene-1-
Yl] propyl 4 - was replaced by [9 [(4-polystyryl butyl) diethyl silyl oxy] nonane-1-oxy] Synthesis advance 1 hour vacuum drying and argon gas benzenesulfonic induction member 4- [9
In a 5 mL cylinder type reactor having-[(4-polystyrylbutyl) diethylsilyloxy] nonane-1-oxy] benzenesulfonyl chloride (250.2 mg, 0.126 mmol in terms of a reactive site), 3 equivalents at room temperature were added. [1
R- [1α (S *), 3aβ, 7aα]]-octahydro-1- (2-hydroxy-1-methylethyl) -7a
-Methyl-4H-inden-4-one (80 mg, 0.3
8 mmol) and a solution of 4- (N, N-dimethylamino) pyridine (62 mg, 0.50 mmol) in dry methylene chloride (1.8 mL) were added. After shaking for 2 hours, the reaction solution was filtered, and the resin was washed with methylene chloride (3 mL × 2).
Unreacted [1R- [1α (S *), 3aβ, 7aα]]
-Octahydro-1- (2-hydroxy-1-methylethyl) -7a-methyl-4H-inden-4-one was recovered. Further, the resin was treated with tetrahydrofuran: water = 3:
1 solution (3 mL), methanol (3 mL), tetrahydrofuran: water = 3: 1 solution (3 mL), methanol (3 mL),
Washed twice each with ether (3 mL). The obtained resin is dried under vacuum for 12 hours, and has the following properties (S) -2-[(1R, 3aR, 7aR) -octahydro-7a-methyl-4-oxo-4H-indene-1-.
The synthesis | combination (269.9 mg, conversion yield with respect to sulfonyl chloride of 90%) of yl] propyl 4- [9-[(4-polystyrylbutyl) diethylsilyloxy] nonane-1-oxy] benzene sulfone derivative was obtained.

¹³ C SR-MAS NMR (400 MHz, CDCl ₃ ) δ 21
1.1, 163.4, 130.1, 125.7, 114.9, 74.9, 68.6, 63.0,
52.5, 49.7 FT-IR (resin) 2905, 1714, 1599, 1494, 1453, 1366,
1262, 1170, 1101, 1029, 967, 837 cm ^-1

Example 6 (S) -2-[(1R, 3aR, 6R, 7aR) -octahydro-6,7a-dimethyl-4-oxo-4H-inden-1-yl] propyl 9-[(4- according to the synthetic example 5 polystyryl butyl) diethyl silyl oxy] nonane-1-oxy] benzenesulfonyl down derivative, 4- [9 - [(4-polystyryl butyl) diethyl silyl oxy] nonane-1-oxy] benzenesulfonyl Chloride (200 mg, 0.101 mmol in terms of reactive site) and (1R, 3aR, 6R, 7aR)-
Octahydro-1-[(S) -2-hydroxy-1-methylethyl] -6,7a-dimethyl-4H-indene-
By using 4-one (68 mg, 0.30 mmol) and 4- (N, N-dimethylamino) pyridine (49 mg, 0.40 mmol), (S) -2-[(1R, 3a) having the following physical properties is obtained.
R, 6R, 7aR) -Octahydro-6,7a-dimethyl-4-oxo-4H-inden-1-yl] propyl 4- [9-[(4-polystyrylbutyl) diethylsilyloxy] nonane-1-oxy A benzenesulfone derivative (217 mg, conversion yield to sulfonyl chloride 92%) was obtained.

¹³ C SR-MAS NMR (400 MHz, CDCl ₃ ) δ 21
0.4, 163.4, 130.1, 114.8, 74.9, 68.6, 63.0, 61.1,
52.3, 49.6, 49.2, 48.0, 7.0, 4.9 FT-IR (resin) 3024, 2935, 1946, 1871, 1803, 1716,
1600, 1493, 1449, 1362, 1263, 1169, 1099, 1027, 9
66 cm ^-1

Example 7 (R) -2-[(1R, 3aR, 7aR) -octahydro-7a-methyl-4-oxo-4H-indene-1-
Yl] propyl 4 - according to the synthetic example 5 [9 [(4-polystyryl butyl) diethyl silyl oxy] nonane-1-oxy] benzenesulfonic induction body, 4- [9 - [(4-polystyryl butyl) Diethylsilyloxy] nonane-1-oxy] benzenesulfonyl chloride (200 mg, 0.101 mmol in terms of a reactive site) and (1R, 3aR, 7aR) -octahydro-1-[(R) -2-hydroxy-1-methylethyl ] -7a-methyl-4H-inden-4-one (6
By using 4 mg (0.30 mmol) and 4- (N, N-dimethylamino) pyridine (49 mg, 0.40 mmol), (R) -2-[(1R, 3aR, 7a) having the following physical properties is obtained.
R) -Octahydro-7a-methyl-4-oxo-4H
-Inden-1-yl] propyl 4- [9-[(4-
Polystyrylbutyl) diethylsilyloxy] nonane-
1-oxy] benzenesulfone derivative (216 mg, conversion yield to sulfonyl chloride 91%) was obtained.

¹³ C SR-MAS NMR (400 MHz, CDCl ₃ ) δ 21
1.1, 163.4, 130.2, 114.8, 73.5, 68.6, 63.0, 61.5,
52.4, 49.4, 12.9, 7.0, 5.0 FT-IR (resin) 3026, 2930, 1944, 1876, 1804, 1714,
1599, 1493, 1452, 1367, 1261, 1167, 1100, 942 cm
^-1

Example 8 4- [9- [6- (polystyrylmethoxymethyl) tetrahydropyranyl-2- oxy] nonane-1-oxy]
Synthesis of benzenesulfonyl chloride
Dihydro-2H-pyran-2-ylmethoxymethyl polystyrene (70.4 mg, 69 μmo in terms of reactive site)
4- (9-Hydroxynonane-1-oxy) at room temperature under an argon atmosphere in a 5 mL cylindrical reactor having
Benzenesulfonyl chloride (48mg, 0.14mmol)
Of dry methylene chloride (0.7 mL) and (+)-10-
Camphor sulfonic acid (1.6 mg, 6.9 μmol) was added sequentially. After shaking at the same temperature for 5 hours, the reaction mixture was filtered and rinsed with dry methylene chloride (2 × 3 mL) to recover unreacted 4- (9-hydroxynonane-1-oxy) benzenesulfonyl chloride. Further, the resin was treated with methylene chloride-triethylamine (3: 1, 3 mL), tetrahydrofuran: water = 3: 1 solution (3 mL), methanol (3 mL), tetrahydrofuran: water = 3: 1 solution (3 m
L), methanol (3 mL) and ether (3 mL) twice each. The obtained resin was dried in vacuum for 12 hours, and 4- [9- [6- (polystyrylmethoxymethyl) tetrahydropyranyl-2-oxy] nonane-1-oxy] benzenesulfonyl chloride (86.5 mg) having the following physical properties was obtained. , 46 μmol).

FT-IR (resin) 3060, 3026, 2938, 1944,
1875, 1804, 1747, 1591, 1493, 1453, 1376, 1311, 1
268, 1170, 834, 761, 699, 571 cm ^-1

Example 9 (S) -2-[(1R, 3aR, 7aR) -octahydro-7a-methyl-4-oxo-4H-indene-1-
Synthesis of yl] propyl 4- [9- [6- (polystyrylmethoxymethyl) tetrahydropyranyl-2-oxy] nonane-1-oxy] benzenesulfone derivative According to Example 5, 4- [9- [6- ( Polystyrylmethoxymethyl) tetrahydropyranyl-2-oxy] nonane-1-oxy] benzenesulfonyl chloride (50.
0 mg, 26.6 μmol in terms of reactive site) and [1R-
[1α (S *), 3aβ, 7aα]]-octahydro-
1- (2-hydroxy-1-methylethyl) -7a-methyl-4H-inden-4-one (17 mg, 81 μm
l) and 4- (N, N-dimethylamino) pyridine (13 m
g, 0.11 mmol), having the following physical properties (S)
-2-[(1R, 3aR, 7aR) -octahydro-7
a-Methyl-4-oxo-4H-inden-1-yl]
Propyl 4- [9- [6- (polystyrylmethoxymethyl) tetrahydropyranyl-2-oxy] nonane-1
[Oxy] benzenesulfone derivative (54.7 mg, 100% conversion yield based on sulfonyl chloride) was obtained.

FT-IR (resin) 3060, 3026, 2973, 1943,
1803, 1710, 1649, 1596, 1493, 1452, 1364, 1307, 1
261, 1174, 820, 757, 697, 564 cm ^-1

[0163] Reference Example 1 [1R- [1α (S * ), 3aβ, 7aα]] - octahydro-1- (2-hydrate proxy-1-methylethyl) -
Synthesis of 7a-methyl-4H-inden-4-one [1R- [1α (S *), 3aβ, 7aα]]-octahydro-1- [2-[(1,1-dimethylethyl) dimethylsilyloxy]- 1-methylethyl] -7a-methyl-4H-inden-4-one (457 mg, 1.41 mm
ol, Literature Doi, T .; Hijikuro, I .; Takahashi, TJA
Hydrogen fluoride pyridine complex (0.5 mL) was added to a solution of m. Chem. Soc. 1999, 121, 6749.) in dry tetrahydrofuran (10 mL) at room temperature under an argon atmosphere, followed by stirring for 6 hours. The reaction mixture was diluted with ethyl acetate and neutralized at 0 ° C. with saturated aqueous sodium hydrogen carbonate. The organic layer and the aqueous layer were separated, and the aqueous layer was extracted with ethyl acetate. The obtained organic matter was washed with 3M hydrochloric acid (twice), saturated aqueous sodium hydrogen carbonate and saturated saline,
It was dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography with 30% ethyl acetate-hexane to give a colorless liquid [1R
-[1α (S *), 3aβ, 7aα]]-octahydro-1- (2-hydroxy-1-methylethyl) -7a-
Methyl-4H-inden-4-one (290 mg, 98
%).

[Α] ³⁰ _D -10.4 ° (c 0.886, CHCl ₃ ); ¹ H NMR (270 MHz, CDCl ₃ ) δ 3.63 (dd, J = 2.6, 10.6
Hz, 1H, H ₂₂ ), 3.41 (dd, J = 6.3, 10.6 Hz, 1H,
H ₂₂ ), 2.45 (dd, J = 7.6, 11.5 Hz, 1H, H ₁₄ ), 1.08
(d, J = 6.3 Hz, 3H, H ₂₁ ), 0.65 (s, 3H, H ₁₈ ); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 212.0, 67.7, 61.8, 5
3.0, 49.9, 41.0, 38.9, 38.4, 27.1, 24.1, 19.2, 16.
9, 12.6; IR (neat) 3420, 2959, 1713, 1460, 1384, 1236, 1044
cm ^-1 ; HRMS (ESI-TOF) (C ₁₃ H ₂₃ O ₂ ), found 211.1698 (M + H)
, Found 211.1695

Reference Example 2 (1R, 3aR, 6R, 7aR) -octahydro-1-
[(S) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -6,7a -dimethyl
(1R, 3aR, 7aR) -2,3,3a, a raw material for the synthesis of tyl -4H-inden-4-one
4,7,7a-Hexahydro-1-[(S) -2-
[(1,1-dimethylethyl) dimethylsilyloxy]
-1-methylethyl] -7a-methyl-4H-inden-4-one has been described in the literature (Doi, T .; Hijikuro, I .; T.
akahashi, TJ Am. Chem. Soc. 1999, 121, 6749.)
Synthesized according to the following procedure. Copper (I) iodide (4.195 g, 2
2.02 mmol) in a dry ether (220 mL) suspension.
Methyllithium (1.05 M ether solution, 41.9 mL, 44.0 mmol) was added dropwise at 0 ° C. under an argon atmosphere.
At the same temperature, (1R, 3aR, 7aR)-
2,3,3a, 4,7,7a-hexahydro-1-
[(S) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7a-methyl-
4H-Inden-4-one (2.368 g, 7.342)
mmol) in dry ether (220 mL). After the reaction solution was stirred at 0 ° C for 30 minutes, buffered water of ammonium chloride and ammonia (about pH 7 to 8,400 mL) was added. After adding ether and extracting the aqueous layer, the extract was washed with saturated saline and dried over anhydrous sodium sulfate. After filtration, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography with 1.7 to 2.5% ethyl acetate-hexane to give a colorless liquid (1R, 3aR, 6R, 7aR).
-Octahydro-1-[(S) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -6,7a-dimethyl-4H-inden-4-one (1.814 g, 73%).

[Α] ¹² _D + 11.7 ° (c 0.801, CHCl ₃ ); ¹ H NMR (270 MHz, CDCl ₃ ) δ 3.56 (dd, J = 〜2, 9.6
Hz, 1H, H ₂₂ ), 3.32 (dd, J = 6.3, 9.6 Hz, 1H, H ₂₂ ),
2.41 (dd, J = 7.6, 11.5 Hz, 1H, H 14), 1.02~1.06
(m, 6H, 11-methyl, H ₂₁ ), 0.89 (s, 9H, SiCMe ₃ ), 0.6
5 (s, 3H, H ₁₈ ), 0.03 (s, 6H, SiMe ₂ ); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 211.5, 67.6, 61.4, 5
3.0, 49.8, 49.5, 48.3, 38.7, 31.9, 27.4, 26.0, 22.
7, 19.1, 18.4, 17.2, 13.4, -5.29, -5.32; IR (neat) 2892, 1696, 1447, 1372, 1243, 1088, 833
cm ^-1

[0167] (1R, 3aR, 6R, 7aR ) - octahydro -1 - [(S) -2- hydroxy-1-methylethyl] -6,7A- dimethyl -4H- inden-4-one synthesis (1R , 3aR, 6R, 7aR) -octahydro-1-
[(S) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -6,7a-dimethyl-4H-inden-4-one (1.794 g, 5.94 g).
To a solution of 298 mmol) in dry tetrahydrofuran (80 mL) was added hydrogen fluoride pyridine complex (4.0 mL) at 0 ° C. under an argon atmosphere, and the mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate, saturated aqueous sodium hydrogen carbonate was added at 0 ° C., and the aqueous layer was separated. The organic layer was washed with 3M hydrochloric acid (twice),
The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, and dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration under reduced pressure was added to 25
(1R, 3aR, 6R, 7aR) -octahydro-1-[(S) -2-hydroxy-1-methylethyl] -6,7a-dimethyl-4H-indene by silica gel column chromatographic purification with% ethyl acetate-hexane. -4-
ON (0.822 g, 69%) was obtained as a colorless liquid.

[Α] ¹² _D + 12.7 ° (c 0.500, CHCl ₃ ); ¹ H NMR (270 MHz, CDCl ₃ ) δ 3.63 (br d, J = 10.6 H
z, 1H, H ₂₂ ), 3.32 (dd, J = 6.3, 10.6 Hz, 1H, H ₂₂ ),
2.41 (dd, J = 7.6, 11.2 Hz, 1H, H ₁₄ ), 1.08 (d, J =
5.9 Hz, 3H, 11-methyl), 1.03 (d, J = 6.3 Hz, 3H,
H ₂₁ ), 0.65 (s, 3H, H ₁₈ ); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 211.3, 67.6, 61.3, 5
2.8, 49.7, 49.4, 48.2, 38.4, 31.8, 27.4, 22.6, 19.
0, 17.0, 13.3; IR (neat) 3326, 2892, 1690, 1442, 1371, 1224 cm ^-1 ; HRMS (ESI-TOF) (C ₁₄ H ₂₅ O ₂ ), Calculated 225.1855 (M + H)
, Found 225.1862

Reference Example 3 (1R, 3aR, 4S, 7aR) -octahydro-4-
[(1,1-dimethylethyl) dimethylsilyloxy]
-1 - [(R) -2- hydroxy-1-methylethyl chill]
Synthesis of -7a -methyl-1H-indene (S) -2-[(1R, 3aR, 4S, 7aR) -octahydro-4-[(1,1-dimethylethyl) dimethylsilyloxy] -7a-methyl-1H -Inden-1-
Il] propanal (4.35 g, 13.4 mmol, literature
Posner, GH; Lee, JK; White, MC; Hutchings,
RH; Dai, H .; Kachinski, JL; Dolan, P .; Kensl
er, TWJ Org. Chem. 1997, 62, 3299.) and a solution of sodium bicarbonate powder (9.02 g, 0.107 mol) in ethanol (200 mL) were stirred at 75 ° C for 7 days. After filtering the reaction solution, the filtrate was washed with water (200 mL).
And the aqueous layer was extracted twice with ether. The extract was washed twice with a saturated saline solution and dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography with 2% ethyl acetate-hexane to give 2-[(1R, 3aR, 4S, 7aR) -octahydro-4-[(1,1-dimethylethyl). ) Dimethylsilyloxy] -7a-methyl-1H-inden-1-yl]
Diastereomer of propanal (3.58 g, 82
%, Non-natural form at steroid number 20: natural form ratio = 6
2:38) as a colorless liquid.

¹ H NMR (270 MHz, CDCl ₃ ) δ 9.57 (d, J
= 3.0 Hz, 0.38H, H ₂₂ natural), 9.54 (d, J = 5.0 H
z, 0.62H, H ₂₂ unnatural), 4.01 (m, 1H, H ₈ ), 2.34
(m, 1H, H ₁₇ ), 1.09 (d, J = 6.9 Hz, 3 x 0.38H, H ₂₁
natural), 0.98 (d, J = 9.6 Hz, 3 x 0.62H, H ₂₁ unna
tural), 0.92 (s, 3 x 0.38H, H ₁₈ natural), 0.88 (s,
3 x 0.62H, H ₁₈ unnatural), 0.87 (s, 9H, SiCMe ₃ ),
0.00 (s, 6H, SiMe ₂ )

2-[(1R, 3aR, 4S, 7aR)-
Octahydro-4-[(1,1-dimethylethyl) dimethylsilyloxy] -7a-methyl-1H-indene-
1-yl] diastereomer of propanal (3.5
Sodium borohydride (0.408) at −78 ° C. in a solution of 0 g, 10.8 mmol, unnatural form at steroid No. 20: natural form ratio = 62: 38) in methanol (80 mL).
g, 10.8 mmol) and stirred at the same temperature for 15 minutes. After adding a saturated ammonium chloride aqueous solution, ether was added for extraction. The extract was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography with 5% ethyl acetate-hexane (1R, 3aR, 4S,
7aR) -Octahydro-4-[(1,1-dimethylethyl) dimethylsilyloxy] -1-[(R) -2-hydroxy-1-methylethyl] -7a-methyl-1H-
Indene (1.97 g, two-step yield 46%) was obtained as a colorless liquid, and 10% ethyl acetate-hexane was used to give (1R, 3aR,
4S, 7aR) -Octahydro-4-[(1,1-dimethylethyl) dimethylsilyloxy] -1-[(S)-
2-hydroxy-1-methylethyl] -7a-methyl-
1H-indene (1.22 g, 28% yield in two steps) was recovered.

[Α]¹⁴ _D + 43.4 ° (c 0.468, CHCl_Three);¹ H NMR (270 MHz, CDCl_Three) δ 3.99 (m, 1H, H₈), 3.71
(dd, J = 3.6, 10.6 Hz, 1H, H_{twenty two}), 3.43 (dd, J = 6.
9, 10.6 Hz, 1H, H_{twenty two}), 0.94 (d, J = 6.6 Hz, 3H,
H_{twenty one}), 0.92 (s, 3H, H₁₈), 0.88 (s, 9H, SiCMe_Three), 0.0
0 (s, 3H, SiMe), -0.01 (s, 3H, SiMe);¹³ C NMR (67.8 MHz, CDCl_Three) δ 69.4, 66.9, 53.15, 5
3.06, 42.0, 40.2, 37.6, 34.5, 26.8, 25.9, 23.0, 1
8.1, 17.7, 16.7, 14.2, -4.7, -5.1; IR (neat) 3254, 2870, 1456, 1363, 1242, 1157, 107
4, 1019, 832, 762 cm^{- 1}; HRMS (ESI-TOF) (C₁₉H₃₈O_TwoSiNa), calc. 349.2539 (M +
Na), found 349.2553

[0173] (1R, 3aR, 4S, 7aR ) - octahydro -1 - [(R) -2- hydroxy Shi-1- methylethyl
Tyl] -7a-methyl-1H-inden-4-ol
Synthesis (1R, 3aR, 4S, 7aR) -octahydro-4-
[(1,1-dimethylethyl) dimethylsilyloxy]
-1-[(R) -2-hydroxy-1-methylethyl]
-7a-methyl-1H-indene (100 mg, 0.30
6 mmol) in methanol (10 mL).
-Camphorsulfonic acid (23 mg, 0.10 mmol) was added and stirred at 55 ° C for 1 day. After diluting the reaction solution with ethyl acetate, the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with 50% ethyl acetate-hexane to give (1R, 3aR, 4S, 7aR) -octahydro-1- as a colorless liquid.
[(R) -2-hydroxy-1-methylethyl] -7a
-Methyl-1H-inden-4-ol (63.7 mg,
98%).

¹ H NMR (270 MHz, CDCl ₃ ) δ 4.06 (m, 1
H, H ₈ ), 3.69 (dd, J = 5.0, 10.6 Hz, 1H, H ₂₂ ), 3.41
(dd, J = 6.9, 10.6 Hz, 1H, H ₂₂ ), 0.931 (s, 3H, H
_{18), 0.929 (d, J} = 6.6 Hz, 3H, H 21); 13 C NMR (67.8 MHz, CDCl 3) δ 69.7, 67.1, 53.5, 53.
0, 42.2, 40.3, 37.9, 34.1, 27.1, 22.9, 18.0, 17.1,
14.4; IR (neat) 3391, 2933, 1471, 1456, 1361, 1264, 788
cm ^-1

(1R, 3aR, 4S, 7aR) -octahydro-1-[(R) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7
Synthesis of a- methylation -1H- inden-4-ol (1R, 3aR, 4S, 7aR ) - octahydro-1
[(R) -2-hydroxy-1-methylethyl] -7a
-Methyl-1H-inden-4-ol (63.0 mg,
0.296 mmol), imidazole (30 mg, 0.44 mm)
ol) in dry methylene chloride (1.5 mL) at 0 ° C. under an argon atmosphere was added tert-butyldimethylsilyl chloride (50 mg, 0.33 mmol). The reaction solution was stirred at the same temperature for 30 minutes and diluted with ether. The solution was washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with 5% ethyl acetate-hexane to give a colorless liquid (1R, 3aR, 4S, 7a).
R) -octahydro-1-[(R) -2-[(1,1-
Dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7a-methyl-1H-inden-4-ol (90.8 mg, 94%) was obtained.

¹ H NMR (270 MHz, CDCl ₃ ) δ 4.07 (m, 1
H, H ₈ ), 3.66 (dd, J = 4.0, 9.6 Hz, 1H, H ₂₂ ), 3.31
(dd, J = 7.3, 9.6 Hz, 1H, H ₂₂ ), 0.93 (s, 3H, H ₁₈ ),
0.889 (d, J = 6.6 Hz, 3H, H ₂₁ ), 0.888 (s, 9H, SiC
Me ₃ ), 0.02 (s, 6H, SiMe ₂ ); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 69.4, 66.8, 53.3, 52.
6, 41.8, 40.0, 37.7, 33.7, 26.5, 26.1, 25.7, 22.5,
17.6, 16.8, 14.0, -5.2, -5.3; IR (neat) 3401, 2931, 2858, 1473, 1361, 1256, 109
2, 835, 775 cm ^-1

(1R, 3aR, 7aR) -octahydro-1-[(R) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7a-methyl- 4H-indene- Synthesis of 4-one (1R, 3aR, 4S, 7aR) -octahydro-1-
[(R) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7a-methyl-
1H-inden-4-ol (90.0 mg, 0.276
mmol) and pyridinium p-toluenesulfone derivative (3.5 mg, 14 μmol) in dry methylene chloride (1.4 mL) at 0 ° C. under an argon atmosphere was added pyridinium dichromate (207 mg, 0.552 mmol). After the reaction solution was stirred at room temperature for 2 hours, it was diluted with ethyl acetate. The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with 2% ethyl acetate-hexane to give a colorless liquid (1
R, 3aR, 7aR) -octahydro-1-[(R)-
2-[(1,1-Dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7a-methyl-4H-inden-4-one (89.3 mg, 100%) was obtained.

[Α] ³⁰ _D -21 ° (c 0.60, CHCl ₃ ); ¹ H NMR (270 MHz, CDCl ₃ ) δ 3.58 (dd, J = 3.6, 9.9
Hz, 1H, H ₂₂ ), 3.45 (dd, J = 5.6, 9.9 Hz, 1H, H ₂₂ ),
2.43 (dd, J = 7.6, 11.2 Hz, 1H, H ₁₄ ), 0.90 (d, J
= 8.6 Hz, 3H, H ₂₁ ), 0.89 (s, 9H, SiCMe ₃ ), 0.63 (s,
3H, H ₁₈ ), 0.03 (s, 6H, SiMe ₂ ); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 212.1, 66.8, 62.0, 5
2.9, 49.8, 41.0, 38.4, 37.7, 26.6, 26.0, 24.1, 19.
0, 18.4, 16.9, 13.0, -5.25, -5.32; IR (neat) 2932, 2886, 2858, 1717, 1472, 1463, 138
5, 1252, 1097, 836, 776 cm ^-1

(1R, 3aR, 7aR) -octahydro-1-[(R) -2-hydroxy-1 -methylethyl]
Synthesis of -7a -methyl-4H-inden-4-one (1R, 3aR, 7aR) -octahydro-1-
[(R) -2-[(1,1-dimethylethyl) dimethylsilyloxy] -1-methylethyl] -7a-methyl-
To a solution of 4H-inden-4-one (60 mg, 0.18 mmol) in methanol (5 mL) at room temperature was added (+)-10-camphorsulfonic acid (14 mg, 60 μmol) and stirred at the same temperature for 30 minutes. After diluting the reaction solution with ethyl acetate, the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with 30% ethyl acetate-hexane to give (1R, 3aR, 7aR) -octahydro-1- as a white solid.
[(R) -2-hydroxy-1-methylethyl] -7a
-Methyl-4H-inden-4-one (37 mg, 96
%).

[Α] ³⁰ _D -18 ° (c 0.67, CHCl ₃ ); ¹ H NMR (270 MHz, CDCl ₃ ) δ 3.68 (dd, J = 3.0, 10.6
Hz, 1H, H ₂₂ ), 3.50 (dd, J = 5.9, 10.6 Hz, 1H,
H ₂₂ ), 2.44 (dd, J = 7.6, 11.2 Hz, 1H, H ₁₄ ), 0.96
(d, J = 6.3 Hz, 3H, H ₂₁ ), 0.64 (s, 3H, H ₁₈ ); ¹³ C NMR (67.8 MHz, CDCl ₃ ) δ 212.0, 67.0, 61.9, 5
2.9, 49.7, 40.9, 38.4, 37.5, 26.7, 24.0, 19.0, 16.
6, 13.0; IR (neat) 3455, 2954, 1686, 1451, 1384, 1311, 127
6, 1050, 1024 cm ^-1

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 309/12 C07D 309/12 // C07F 7/08 C07F 7/08 Q 7/12 7/12 VF Term (reference) 4C062 AA22 4H006 AA01 AA02 AB84 AC43 TB32 4H049 VN01 VP01 VQ53 VR23 VR41 VU20 4J100 AB07P BA02P BA15P BA16P BA51P BA58H BA58P BA72H BA76P BB01H BB01P BC52H BC53P CA51 CA31 HA61

Claims (16)

[Claims] (1) Formula (A): Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. Atom, a nitrogen atom, a sulfur atom, or a halogen atom, and may have a substituent which may include those atoms), and R ¹⁰¹ represents a group which may have a substituent. R ¹⁰² and R ¹⁰³ each independently represent an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have a substituent). The sulfone derivative shown. 2. Formula (B): Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. R ¹⁰⁴ may have an atom, a nitrogen atom, a sulfur atom, or a halogen atom, or may have a substituent which may include those atoms), and R ¹⁰⁴ is a polystyrene optionally having a substituent. And n is an integer of 0 to 2). 3. Formula (C): (Wherein, R ¹⁰⁵ represents a residue of a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent;
Is an integer of 2 to 20). 4. Formula (D): Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. Atom, a nitrogen atom, a sulfur atom, or a halogen atom, and may have a substituent which may include those atoms), and R ¹⁰¹ represents a group which may have a substituent. R ¹⁰² and R ¹⁰³ each independently represent an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have a substituent); ¹⁰⁶ is an alkyl group,
An alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above group may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, or may have a substituent which may contain those atoms) Sulfone derivatives represented by: 5. A compound of the formula (E): Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. R ¹⁰⁴ may have an atom, a nitrogen atom, a sulfur atom, or a halogen atom, or may have a substituent which may include those atoms), and R ¹⁰⁴ is a polystyrene optionally having a substituent. R ¹⁰⁶ represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom, and May have a substituent that may be contained), and n is 0
A sulfone derivative represented by the formula: 6. Formula (F): (Wherein, R ¹⁰⁵ represents a polymer residue having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent,
¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups are an oxygen atom,
(It may have a nitrogen atom, a sulfur atom, a halogen atom, and may have a substituent which may contain those atoms.)
Wherein m is an integer of 2 to 20). 7. A polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent, and a compound represented by the formula (G): (Wherein R ¹⁰⁰ ′ has an alkyl group having a hydroxyl group, an alkenyl group having a hydroxyl group, an alkynyl group having a hydroxyl group, an aryl group having a hydroxyl group, or a hydroxyl group. Aralkyl groups (the above groups are oxygen atoms,
(It may have a nitrogen atom, a sulfur atom, a halogen atom, and may have a substituent which may contain those atoms.)
With a compound of the formula (H): in the presence of an acid or a base. Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. R ¹⁰⁵ may have an atom, a nitrogen atom, a sulfur atom, or a halogen atom, or may have a substituent which may contain those atoms), and R ¹⁰⁵ is a reactive functional group capable of bonding to a hydroxyl group. And a polymer residue which may have a substituent). 8. A compound of formula (I):[Wherein, R¹⁰¹ Is a polymer residue which may have a substituent
And R¹⁰² And R^{Ten Three} Are, independently,
Group, alkenyl group, alkynyl group, aryl group or
Is an aralkyl group (the above groups may have a substituent
Y is a group reactive with a hydroxyl group, and is a hydrogen atom.
, Halogen atom, alkylsulfonyl group, alkenyl
Sulfonyl group, alkynyl sulfonyl group, aryl sulf
Represents a honyl group or an aralkylsulfonyl group]
And the compound of the formula (G)
In the presence, the compound is reacted with a compound of the formula (A):(Where R¹⁰⁰ And R¹⁰¹ And R¹⁰² And R¹⁰³ Is before
(As defined above).
Item 8. The method according to Item 7. 9. A sulfone derivative having a chlorosulfonyl group by reacting a polymer having a vinyloxy moiety and optionally having a substituent with the compound of the formula (G) in the presence of an acid. The method of claim 7 for producing. 10. A sulfone derivative having a chlorosulfonyl group produced by the method according to claim 9. Description: 11. The formula (J): (Wherein R ¹⁰⁴ represents a polystyrene chain which may have a substituent, and n is an integer of 0 to 2) and the compound of the above formula (G) in the presence of an acid. And reacting with formula (B): (Wherein, R ^100, R ¹⁰⁴ and n are as defined above) The method according to claim 7 for producing a sulfone derivative of. 12. A polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent,
Formula (K): (Wherein m is an integer of 2 to 20) in the presence of an acid or a base to react with a compound of the formula (C): (Wherein, R ¹⁰⁵ represents a residue of a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent;
Is an integer of 2 to 20). 13. The formula (L): (Wherein, R ¹⁰⁶ represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group
Which may have an oxygen atom, a nitrogen atom, a sulfur atom, and a halogen atom, and may have a substituent which may contain these atoms) and a compound represented by the formula (A): Formula 16 Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. Atom, a nitrogen atom, a sulfur atom, or a halogen atom, and may have a substituent which may include those atoms), and R ¹⁰¹ represents a group which may have a substituent. Represents a coalescing residue, and R ¹⁰² and R ¹⁰³ are
A polymer represented by an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups may have a substituent) independently in the presence of a base, The reaction is carried out to obtain a compound of the formula (D): (Wherein R ¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups are
R ¹⁰⁰ , R ¹⁰¹ , R ¹⁰² and R ¹⁰³ which may have an oxygen atom, a nitrogen atom, a sulfur atom, a halogen atom and may have a substituent which may contain those atoms.
Is as defined above). 14. The formula (L): (Wherein R ¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups are
Which may have an oxygen atom, a nitrogen atom, a sulfur atom, and a halogen atom, and may have a substituent which may contain those atoms) and a compound represented by the formula (B): Chemical formula 19 Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. R ¹⁰⁴ may have an atom, a nitrogen atom, a sulfur atom, or a halogen atom, or may have a substituent which may include those atoms), and R ¹⁰⁴ is a polystyrene optionally having a substituent. And n is an integer of 0 to 2) in the presence of a base to give a compound of the formula (E): (Wherein R ¹⁰⁰ , R ¹⁰⁴ , R ¹⁰⁶ and n are as defined above). 15. Formula (L): (Wherein R ¹⁰⁶ is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group (the above groups are
Which may have an oxygen atom, a nitrogen atom, a sulfur atom, and a halogen atom, and may have a substituent which may contain those atoms) and a compound represented by the formula (C): Formula 22 (Wherein, R ¹⁰⁵ represents a residue of a polymer having a reactive functional group capable of binding to a hydroxyl group and optionally having a substituent;
Is an integer of 2 to 20) with a compound represented by the formula (F): (Wherein R ¹⁰⁵ , R ¹⁰⁶ and m are as defined above). 16. Formula (N): (Wherein, R ¹⁰⁷ , R ¹⁰⁸ and R ¹⁰⁹ each independently represent an alkyl group, alkenyl group, alkynyl group, aryl group, aralkyl group, alkyloxy group, alkenyloxy group, alkynyloxy group, aryloxy group or aralkyl An oxy group (the above groups may have a substituent), or a hydrogen atom or a hydroxyl group, or an acetal compound which may have a substituent by two groups of R ¹⁰⁸ and R ¹⁰⁹ X and Z may each independently form a hydrogen atom, a hydrogen atom,
A hydroxyl group or an ether group, an ester group or a silyloxy group derived from the hydroxyl group, or X and Z taken together represent an oxygen atom, a ketal group or an optionally protected cyanohydrin group) A derivative and a compound represented by the formula (H): Wherein R ¹⁰⁰ is an alkyl group having an oxygen function,
An alkenyl group having an oxygen functional group, an alkynyl group having an oxygen functional group, an aryl group having an oxygen functional group, or an aralkyl group having an oxygen functional group. R ¹⁰⁵ may have an atom, a nitrogen atom, a sulfur atom, or a halogen atom, or may have a substituent which may contain those atoms), and R ¹⁰⁵ is a reactive functional group capable of bonding to a hydroxyl group. A) a compound represented by the formula (P): ## STR26 ## in the presence of a base. (Where R ¹⁰⁰ , R ¹⁰⁵ , R ¹⁰⁷ , R ¹⁰⁸ , R ¹⁰⁹ , X
And Z are as defined above).