CS255854B2 - A method for producing α-sulfonyloxycetone acetals - Google Patents

Abstract

Method for the production of acetates of oc-sulfonyloxy ketones of the general formula II OR3 OSO., -R5 1 i 2 1 Ar - C - CH - R (II), OR4 and optionally their diastereomers, compounds of the general formula V. in which 0 X II 1 i Ar - C - CH - R (V), are converted into compounds of the general formula VI OR3 OH Ar - é - CH - R1 (VI) OR4 which are then reacted with a compound of the general formula R5 - SO2_Hal or (R5 - SC>2)20. Compounds of the general formula II represent new intermediates for the production of alkanoic acids substituted in the -position by an aromatic group, which are useful in the pharmaceutical field and in agriculture.

Description

The invention relates to a process for the production of novel compounds of formula II

OR ³ 0S0 _o -R ⁵

I ^{1 2} 1

Ar - C - CH - R

Ir ⁴ acetals of alpha-sulfonyloxyketones general(II), in which Ar represents

a) a phenyl group which may be substituted by a halogen atom, a C ₁ -g -alkyl group, a C 1 -g -alkoxy group, a C 1 -g -alkanoylamino group, a C 1 -g -haloalkyl group, a phenyl group or a 1-oxo-2-isoindolinyl group,

b) a naphthyl group which may be substituted by a C 1-4 alkoxy group or

c) a thienyl group, R* represents a hydrogen atom or a C,,-alkyl group or Ar and 1—o 2 4

R may form a fused ring with the carbon atom to which they are attached, R and R independently represent a C1-6-alkyl group or together represent a C2-6-alkylene group, r5 represents a 6-alkyl group, a phenyl group which may be substituted by a halogen atom or a C1-6-alkyl group, or a camphoryl group, and optionally their diastereomers.

The compounds of general formula II are novel compounds that have not been described in the literature. They represent novel intermediates that can be used as starting materials in the process for the production of alkanoic acids substituted in the alpha position with an aromatic group according to patents No. 255,851 and No. 255,853. The alkanoic acids mentioned are useful in the pharmaceutical field (e.g. as anti-inflammatory agents) and in agriculture (e.g. as insecticides).

The process for producing new compounds of the above-mentioned general formula II is carried out according to the invention by reacting a compound of the general formula V

About X

Ar - C - Íh - R ¹ (V) , in which X represents a halogen atom and Ar and R ³ have the above meaning, with an alkali metal alkoxide of the general formula r ³ om, β

where M represents an alkali metal and R has the above meaning, whereby for the preparation of compounds of general formula II, where R ³ and R ⁴ have the same meaning, Ar, R ³ and R ⁵ have the above meaning, the reaction of the above compound of formula V is carried out in the presence of an alcohol of general formula

R ³ OH, where R ³ has the meaning given above, to form a compound of general formula VI

OR OH

Ar

I 4 OR (VI) , where R ³ and R ⁴ have the same meaning and represent a C. .-alkyl group. Ar and R ³ have the above-mentioned 3 4 meaning, and for the preparation of compounds of general formula II, where R and R are different and represent a C. .-alkyl group, Ar, R^ and have the above-mentioned meaning, for the reaction of the above-mentioned compound of formula V with the said alkali metal alkoxide V2 nickel epoxy compound of general formula VII

STEED

Ar C - CH \ /

About (VII),

3 where Ar, R and R have the meanings given above, is reacted with an alcohol of the general formula

R OH, where R ⁴ has the above meaning, in the presence _of an alkali metal alkoxide of the general formula

R OM, where R ⁴ has the above meaning and M represents an alkali metal, to form a compound of general formula

4 1 of formula VI, where R and R are different and represent a _C ² -C 6 -alkyl group. Ar and R have the meanings given above, and optionally for the preparation of compounds of general formula II, where R and R together represent a C ₂ -C ₆ -alkylene group, Ar, R and R have the meanings given above, the compound of the above formula *V is reacted with an alkylene glycol of the general formula

HO - R - OH, where R represents a C ₂ _ ₆ -alkylene group, to form a compound of general formula VI, where R and

R ⁴ together represents a C ₉ _ _t; -alkylene group. Ar and R ¹ have the above meaning, and the resulting ^Zb vvi , , 34 compounds of general formula VI, in which Ar and R have the above meaning, R and R independently of each other represent a C|_^-alkyl group or together represent a C ₂ _g-alkylene group, are reacted with a compound of general formula

R ⁵ - SO 2 - Hal or (R ⁵ - SO 2 ) ₂ O, where R 5 has the above meaning and Hal represents a halogen atom.

In the compounds of the above general formulas II and V, the substituent Ar in the broadest sense may include groups derived from cyclic compounds having aromatic character.

The groups can therefore generally be classified as aryl groups, which optionally contain

And at least one substituent and heteroaromatic groups.

a) Aryl groups, optionally containing at least one substituent

The substituent Ar includes, for example, phenyl, biphenyl and naphthyl groups.

Phenyl groups in the meaning of Ar may be unsubstituted or may contain one or more substituents on the aromatic ring. Specific examples of substituents include halogen atoms such as chlorine, bromine, fluorine and iodine, alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, alkoxy groups such as methoxy, ethoxy, n-propoxy-isopropoxy, haloalkyl groups such as trifluoroethyl and trifluoropropyl, heterocyclic groups such as oxo-isoindolinyl groups, alkanoylamino groups such as acetylamino and propionylamino.

Naphthyl groups in the meaning of Ar may be substituted by alkoxy groups, preferably by methoxy groups.

Preferably, 1 to 5 of the said substituents, especially 1 to 3, can be bonded to the aromatic ring.

Specific examples of phenyl and naphthyl groups having substituents on the aromatic ring include chlorophenyl, fluorophenyl, bromophenyl, iodophenyl, tolyl, ethylphenyl, isopropylphenyl, isobutylphenyl, tert-butylphenyl, methoxyphenyl, ethoxyphenyl, isopropoxyphenyl, trifluoroethylphenyl, oxo-isoindolinylphenyl, acetylaminophenyl, fluorobiphenyl, acetylaminobiphenyl, and methoxynaphthyl.

b) Heteroaromatic groups

In the meaning of the substituent Ar, the heteroaromatic group may be a thienyl group.

The alkyl groups in the compounds of formulae II, V, VI and VII may be straight-chain or branched. Examples of such groups include straight-chain or branched alkyl groups having 1 to 6 carbon atoms, especially methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isoamyl and n-hexyl.

The alkoxy groups and alkanoyl groups in the compounds of formulae II, V, VI and VII have no more than 6 carbon atoms, preferably no more than 4 carbon atoms.

The alkylene groups in the compounds of formulae II and VI are preferably ethylene, propylene, butylene, trimethylene or tetramethylene.

As a camphoryl group in the meaning of the substituent R, a D- or L-10-camphoryl group may be mentioned.

Various groups of compounds of the above general formula II are given below as examples.

Preferred aromatic groups Ar are those of the formula R ³ - Ar ³ , in which Ar ³ represents a phenylene or naphthylene group and R ³ represents a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 haloalkyl group, a C 1-6 alkanoylamino group, an oxoindolinyl group, or a phenyl group. Another preferred example of an aromatic group Ar is a thienyl group.

Suitable R ³ groups are C 1-6 -alkyl groups such as methyl, ethyl, n-propyl, isopropyl or butyl. A preferred set of values for the substituent R ³ are hydrogen and C 1-6 -alkyl groups.

C1-8 alkyl groups are suitable as the alkyl groups represented individually by ^R3 and ^R4 . As the alkylene group formed by ^R3 and ^R4 together, _{a C2-12} alkylene group such as ethylene, propylene and trimethylene is suitable.

Examples of suitable alkyl groups represented by R ³ include unsubstituted C 1-6 -alkyl groups such as methyl, ethyl, butyl and further D- or L-10-camphoryl is preferred as the R ³ group. Preferred aromatic groups R ³ are substituted or unsubstituted phenyl groups of the general formula wherein R ³ represents a hydrogen atom, a halogen atom or a C 1-6 -alkyl group.

Of the compounds of general formula IX prepared by the process according to the invention, those of the following compounds of general formula 1-1 are preferred.

Ar.2

(ί-D ,

6 1 1 in which Ar represents a group of the formula R - Ar - or a thienyl group, R represents a hydrogen atom or a C1-C6-alkyl group, R ³ and R ⁴ independently of each other represent a C1-C6-alkyl group *

or together represent a C2-12 ^alkyl group, R represents a C1-8 alkyl group, a D- or L-10 camphoryl group or a group of the general formula

7 and Ar , R 0 and R 1 have the meanings given above.

In a compound of formula II, Ar and R^ may form a fused ring together with the carbon atom to which these groups are attached. A particular example of a compound of formula II in which Ar and R together form a fused ring is a compound of formula

R ^J 0,

OR ⁴

OSO ₂ -R ^and

Compounds of general formula II according to the invention can be prepared by synthesis from alpha-haloketones of general formula V

X

Ií I i

Ar - C - CH - R (V), in which X represents a halogen atom and Ar and have the meanings given above, by the process shown in 3 in this reaction scheme:

.1

X 1' ¹ Ar - C - CH - R

R O M

STEED

R ³ OH OR ³ OH R ⁵ - S0 ₂ - Hal j 0S0 ₂ ~ R ⁵

Ar - C - CH - R ¹ or (R ⁵ SO_)-0 Ar - C - - R ¹ | δ _ ² 4-> . (II)

OR (VI) .

OR (VII)

In the above reaction scheme, M represents an alkali metal, Hal represents a halogen atom, especially a chlorine atom, and Ar, R 1 , R 2 , R 3 , R 4 and X have the meanings given above.

Compounds of general formula V can be readily prepared by reacting a compound of general formula VIII

X

AND

R - CH - COCl (VIII)-, where R and X have the meanings given above, is subjected to a Friedel-Crafts reaction with a compound of general formula IX

Ar - H (IX) , where Ar has the above meaning, or by halogenation of a compound of the general formula X 0 "1 where Ar and R ³ have the above meaning, which is carried out in a manner known per se.

The procedure from the above reaction scheme is described in detail below.

Grade V—>VI

This step represents the action of an alkali metal alkoxide of the general formula R^OM on a compound of the general formula V in the presence of the corresponding alcohol of the general formula R OH to form an acetal of the alpha-hydroxyketone of the general formula VI. In the compound of the general formula VI produced in this step, R has the same meaning as . Lithium, sodium and potassium alkoxides can be conveniently used as alkali metal alkoxides. The use of sodium alkoxides is advantageous because of their low cost. The amount of alkali metal alkoxides is generally at least 1 mole per 1 mole of the compound of the general formula V. The reaction can be completed quickly if this substance is used in an amount of 1.5 to 3 moles per 1 mole of the compound of the general formula V. The amount of alcohol, which must also be present, can be at least 1 mole per 1 mole of the compound of the general formula V. The alcohol is preferably used in excess so that it also serves as a solvent. It is also possible to add an aprotic solvent that does not participate in the reaction, such as diethyl ether, tetrahydrofuran, DMF or 1,2-dimethoxyethane. The reaction proceeds smoothly at a temperature in the range of -20 to about 100°C. For simplicity of the procedure, the reaction is preferably carried out at room temperature to 60°C.

Alternatively, this step can be carried out by reacting a compound of formula V with an alkali metal alkoxide of formula R OM in an aprotic solvent such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane to form an epoxy compound of formula VII which is then reacted with an alcohol of formula R^OH in the presence of a catalytic amount of alkali metal alkoxide of formula R ⁴ 0M to give an alpha-hydroxy ketone acetal of formula VI (see Examples 8 and 9). A compound of formula VI in which R is different from R can be prepared by this procedure.

The reaction of a compound of formula V with an alkali metal alkoxide of formula R^OM can usually be carried out at a temperature in the range of about 0 to 60 °C using 1 to 3 moles of alkali metal alkoxides per 1 mole of compound of formula V. The reaction of a compound of formula VII with an alcohol of formula R^OH can usually be carried out at a temperature in the range of about 0 to 100 °C using at least 1 mole of alcohol per 1 mole of compound of formula VII.

Alcohol is preferably used in excess to also serve as a solvent.

In yet another alternative to this step, an alpha-haloketone of formula V is reacted in the presence of a dihydric alcohol such as ethylene glycol, propylene glycol or 1,3-propanediol with an alkali metal monosalt of the alcohol to form an alpha-hydroxyketone acetal of formula VI. This procedure provides a product of formula VI in which R and R together form ^{a C2-12} alkylene group, ^ethylene , propylene or trimethylene (see Example 55).

The reaction can usually be carried out at a temperature of 0 to 100 ° C using at least 1 mole, preferably 1.5 to 3 moles, of the alkali metal monosalt of the dihydric alcohol in the presence of at least 0.5 mole, preferably 2 to 10 moles, of the dihydric alcohol. An aprotic solvent not participating in the reaction, such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane, can be added to the reaction medium.

The compounds of general formula VI obtained in the above step, where Ar has a meaning other than phenyl or 4-chlorophenyl group, as well as the compounds of the above formula, where R ¹ has a meaning other than hydrogen atom, are new substances, not yet described in the literature.

Typical examples of such compounds of general formula VI are given below in addition to the compounds described in the examples: e.g. a compound of general formula VI in which Ar is 2-fluoro-4-biphenylyl, R ¹ is methyl, Ar is 2-acetylamino-4-biphenylyl, R 2 is methyl, Ar is 4-chlorophenyl, R 3 is isopropyl.

Grade VI-*II

This step involves the action of an O-sulfonylating agent of the general formula R - SO 2 - Hal ^Z or of the general formula (R 802) 2° ^{on the acetal of} the alpha-hydroxyketone of the general formula VI, obtained in the above step, to form a compound of the general formula II.

Examples of the O-sulfonylating agent are aromatic-substituted sulfonyl halides such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-bromobenzenesulfonyl chloride, p-nitrobenzenesulfonyl chloride and naphthalenesulfonyl chloride, as well as alkanesulfonyl halides or alkanesulfonic acid anhydrides such as methanesulfonyl chloride, butasulfonyl chloride, methanesulfonic anhydride, trifluoromethanesulfonic anhydride, trifluoromethanesulfonyl chloride and L- and D-10-camphorsulfonyl chloride.

The reaction is conveniently carried out under neutral to basic conditions and from this point of view the reaction is preferably carried out in the presence of at least 1 mole of a tertiary amine, such as triethylamine, pyridine or 4-dimethylaminopyridine, per 1 mole of the compound of the general formula VI. In this way the reaction can be carried out at a relatively low temperature in the range of about 0 ° C to room temperature. It is also possible to add an aprotic solvent not participating in the reaction, such as methylene chloride or diethyl ether.

As described above, the compound of formula II prepared by the process of the invention can be prepared in 2 steps from the alpha-haloketone of formula V. This compound can also be prepared by other methods. Such methods include the oxidation of a 1-acetoxy-1-alkene substituted in the 1-position with an aromatic group, of formula XI _n 3

STEED

AND

C

Ar(XI)z

3 where Ar, R, R have the above-mentioned meaning, to form an epoxy compound of general formula VII, the production of an acetal of an alpha-hydroxyketone of general formula VI from the epoxy compound of general formula VI and a further embodiment of step VI—>11, wherein this process comprises acetalization of the corresponding alpha-sulfonyloxyketone to a compound of general formula II, and a method consisting in reducing an acetal of an alpha-oxoketone of general formula XII

OR ³ 0

Ar - C - CR ¹ (XII),

OR ⁴ where Ar, R ¹ , R ³ and formula VI and its

R have the above meaning, to form the acetal of the alpha-hydroxyketone of the general processing in step VI—>11.

The acetal of alpha-sulfonyloxyketone of general formula II can also be produced by various easy methods in a smaller number of steps.

The following examples illustrate the invention in detail.

Example 1

19.0 g of p-isobutylpropiophenone is dissolved in a mixture of 15 ml of anhydrous diethyl ether and 15 ml of anhydrous dioxane and the solution is stirred at room temperature. 17.6 g of bromine is added dropwise to the solution over 25 min and the mixture is stirred for 2.5 hours. Then 50 ml of water is added and the mixture is extracted 3 times with 20 ml of diethyl ether. The extract is washed 4 times with 50 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is dissolved in 30 ml of hot methanol and cooled to -40 °C. The precipitate is filtered off and washed with cold methanol. 21.88 g of alpha-bromo-p-isobutylpropiophenone is obtained in the form of colorless crystals. The yield is 81%.

Melting point: 63 to 66 °C.

IC (KBr): 2950, 1680, 1608, 1419, 1260, 1250, 1167, 955, 862 cm ¹ .

NMR (CDCl ₃ ): delta 0.91 (6H, d, J = 7 Hz), 1.87 (3H, d, J = 7 Hz), 1.8 to 2.2 (1H, m), 2.52 (2H, d, J = 7 Hz), 5.25 (1H, q, J = 7 Hz), 7.22 (2H, d, J = 9 Hz), 7.92 (2H, d, J = 9 Hz) .

Analysis for C 12 H 18 OBr calculated: 58.00% C, 6.37% H, 29.69% Br, found: 57.80% C, 6.27% H, 29.42% Br.

Example 2

1.134 g of sodium methoxide is dissolved in 20 ml of anhydrous methanol and the solution is stirred at room temperature under an argon atmosphere. 20 ml of a solution of 2.692 g of alpha-bromo-p-isobutylpropiophenone in anhydrous methanol is added dropwise to the solution over 30 minutes at room temperature. Then 50 ml of water is added to the reaction mixture and the mixture is extracted 3 times with 20 ml of diethyl ether. The extract is washed with 20 ml of water, dried with anhydrous magnesium sulfate and potassium carbonate and evaporated under reduced pressure in the presence of a small amount of potassium carbonate. 2.370 g of alpha-hydroxy-p-isobutylpropiophenone dimethyl acetal is obtained in the form of a colorless oily substance.

The yield is 94%. For elemental analysis, the product is purified by column chromatography (Florisil, methylene chloride).

IR (neat): 3500, 2950, 1460, 1100, 1050, 980, 850, 800, 740 cm' ¹ ,

NMR (CDCl ₃ ): delta 0.91 (6H, d, J = 7 Hz), 0.96 (3H, d, J = 7 Hz), 1.6 to 2.1 (1H, m),

2.43 (2H, d, J = 7 Hz), 2.57 (1H, broad s), 3.20 (3H, s), 3.30 (3H, s), 4.06 (1H, q, J = 7 Hz), 7.08 (2H, d, J = 9 Hz), 7.33 (2H, d, J = 9 Hz).

Analysis for ^: calculated: 71.39% C, 9.59% H, found: 71.39% C, 9.48% H.

Example 3

9.81 g of p-toluenesulfonyl chloride is dissolved in 10 ml of anhydrous pyridine and the mixture is stirred at room temperature. 10 ml of a solution of 6.65 g of alpha-hydroxypropiophenone dimethyl acetal in anhydrous pyridine is added dropwise to the solution over 10 minutes and the mixture is stirred for 48 hours. The reaction mixture is poured into 200 ml of ice water and stirred for 2 hours. The resulting precipitate is filtered off, washed with water and dried under reduced pressure with potassium hydroxide. 10.91 g of alpha-(p-toluenesulfonyloxy)propiophenone dimethyl acetal is obtained as colorless crystals. The yield is 92%.

Melting point: 62 to 63 °C (from ligroin).

IR (KBr): 1,360, 1,190, 1,175, 1,090, 1,060, 1,040, 910, 710 cm ^-1 .

NMR (CDCl ₃ ): delta 1.07 (3H, d, J = 6 Hz), 2.73 (3H, s), 3.08 (3H, s)i, 3.15 (3H, s) 4.95 (1H, q, J = 6 Hz), 7.33 (7H, m), 7.77 (2H, d, J = 9 Hz).

Analysis for ^c i8 ^R 22°5® ^! calculated: 61.70% C, 6.33% H, 9.15% S, found: 61.72% C, 6.26% H, 9.19% S.

Example 4

26.84 g of isobutylbenzene and 29.34 g of aluminum chloride are stirred in 20 ml of carbon disulfide under ice cooling. 40.63 g of alpha-chloropropionyl chloride are added dropwise to the mixture over 30 minutes and the mixture is stirred under ice cooling for 1.5 hours and then for a further 30 minutes at room temperature. The reaction mixture is poured onto 200 ml of ice water and 100 ml of concentrated hydrochloric acid are added. The mixture is extracted 4 times with 100 ml of diethyl ether. The extract is washed with 100 ml of water and then 4 times with 50 ml of saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue is dissolved in 40 ml of methanol at elevated temperature, treated with activated carbon and cooled to -40 °C. The precipitated crystals are filtered off and washed with cold methanol, yielding 17.83 g of alpha-chloro-p-isobutylpropiophenone in the form of colorless crystals with a melting point of 51-53° C. The yield is 40%.

IR (KBr): 2,950, 1,690, 1,608, 1,419, 1,357, 1,266, 1,180, 956, 861 cm ^-1 .

NMR (CDCip: delta 0.91 (6H, d, J = 7 Hz), 1.71 (3H, d, J = 7 Hz), 1.5 to 2.2 (1H, m),

2.52 (2H, d, J = 7 Hz), 5.20 (1H, q, J = 7 Hz), 7.23 (2H, d, J = 9 Hz), 7.91 (2H, d, J = 9 Hz).

Analysis for C^^H^^OCl:

calculated: 69.47% C, 7.63% H, 15.78% Cl, found: 69.56% C, 7.44% H, 15.76% Cl.

Example 5

In 10 ml of anhydrous methanol, 0.979 g of sodium methoxide is dissolved and the solution is stirred at room temperature under an argon atmosphere. Over 20 minutes, 10 ml of a solution of 2.036 g of alpha-chloro-isobutylpropiophenone in anhydrous methanol is added dropwise to the solution and the mixture is further stirred at room temperature for 4 hours. After the usual work-up described in Example 4, 2.158 g of alpha-hydroxy-p-isobutylpropiophenone dimethyl acetal are obtained in the form of a light yellow oil. The yield is 95%.

Example 6 By a similar procedure to Example 3, alpha-(p-toluenesulfonyloxy)-p-isobutylpropiophenone dimethyl acetal was prepared from alpha-hydroxy-p-isobutylpropiophenone dimethyl acetal in the form of colorless crystals. The yield was 89%.

Melting point: 64-65°C (from hexane).

IC (KBr): 2960, 1360, 1185, 1090, 1050, 930, 915, 780 cm ¹ .

NMR (CDCl ₃ ): delta 0.88 (6H, d, J = 7 Hz), 1.09 (3H, d, J = 7 Hz), 1.5 to 2.1 (1H, m), 2.40 (3H, s), 2.42 (2H, d, J = 7 Hz), 3.07 (3H, s), 3.15 (3H, s) 4.93 (1H, q, J = 7 Hz)

6.9 to 7.4 (6H, m), 7.72 (2H, d, J = 9 Hz).

Analysis for ^C 22 ^H 30°5 ^S: calculated: 64.99% C, 7.44% H, 7.89% S, found: 64.78% C, 7.26% H, 7.93% S.

Example 7

In 5 ml of anhydrous pyridine, 2.94 g of methanesulfonyl chloride are dissolved and the solution is stirred under ice-cooling. Over 15 minutes, 10 ml of a solution of 3.23 g of alpha-hydroxy-p-isobutylpropiophenone dimethylacetal in anhydrous pyridine are added dropwise to the solution. The mixture is stirred under ice-cooling for one hour and then at room temperature for 30 minutes. 30 ml of water are added to the mixture and stirred for 1 hour. The mixture is extracted 3 times with 10 ml of methylene chloride, the extract is washed 3 times with 10 ml of water, dried with anhydrous magnesium sulfate and evaporated in the presence of a small amount of anhydrous potassium carbonate. The oily residue is purified by column chromatography (Florisil, methylene chloride): 3.347 g of alpha-(methanesulfonyloxy)-p-isobutylpropiophenone dimethylacetate are obtained as a colorless oil. The yield is 79%.

iC (neat): 2960, 1350, 1175, 1095, 1065, 1040, 915 cm ^-1 .

NMR (CDCl1): delta 0.88 (6H, d, J = 7 Hz), 1.16 (3H, d, J = 7 Hz), 1.6 to 2.1 (1H, m), 2.44 (2H, d, J = 7 Hz), 3.06 (3H, s), 3.18 (3H, s), 3.26 (3H, s), 4.95 (1H, q, J = = 7 Hz), 7.10 (2H, d, J = 8 Hz), 7.32 (2H, d, J = 8 Hz).

Analysis for ^c i6 ^H 26°5 ^S: calculated: 58.16% C, 7.93% H, 9.69% S, found: 58.06% C, 7.80% H, 9.60% S.

Example 8

9.20 g of sodium methoxide are suspended in 10 ml of anhydrous diethyl ether and the solution is stirred under an argon atmosphere with ice cooling. 80 ml of a solution of 15.0 g of alpha-bromo-p-methoxypropiophenone in anhydrous diethyl ether are added dropwise to the solution over a period of 40 minutes. After the addition is complete, the insoluble material is filtered off in a stream of argon. The filtrate is evaporated under reduced pressure to obtain 7.88 g of 1-(4-methoxyphenyl}-1-methoxy-1,2-epoxypropane as a light red oil. The yield is 68%.

NMR (CDCl ₃ ): delta 1.00 <3H, d, J = 6 Hz), 3.23 (3H, s), 3.52 (1H, q, J = 6 Hz), 3.82 (3H, s) 6.92 (2H, d, J = 7 Hz), 7.38 (2H, d, J = 7 Hz).

Example 9

In 30 ml of anhydrous methanol, 7.88 g of 1-(4-methoxyphenyl)-1-methoxy-1,2-epoxypropane and 200 mg of sodium methoxide are stirred at room temperature for 15 hours. 50 ml of water are added to the reaction solution and the mixture is extracted 3 times with 20 ml of diethyl ether. The extract is dried with anhydrous magnesium sulfate and anhydrous potassium carbonate and evaporated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate. 8.26 g of alpha-hydroxy-p-methoxypropiophenone dimethyl acetal are obtained as a colorless oil. For elemental analysis, this product is purified by column chromatography (Florisil, methylene chloride). The yield is 61%.

IC (neat): 3520, 1050 cm ^-1 .

NMR (CDClg): delta 0.94 (3H, d, J = 7 Hz), 2.35 (1H, d, J = 4 Hz), 3.20 (3H, s), 3.33 (3H, s) 3.78 (3H, s), 4.05 (1H, dq, J = 7 Hz), 6.18 (2H, d, J = 9 Hz), 7.35 (2H, d, J =

= 9 Hz) . Analysis for C-^Hj 8°4’ calculated: 63.70 % C, 8.02 % H found: 63.98 % C, 8.08 % H Example 10

2.67 g of p-toluenesulfonyl chloride is dissolved in 5 ml of anhydrous pyridine and the solution is stirred at room temperature. To the solution is added dropwise 5 ml of a solution of 1.58 g of alpha-hydroxy-p-methoxypropiophenone dimethyl acetal in anhydrous pyridine over 10 minutes and the mixture is stirred for 72 hours.

About 20 g of ice-water are added to the mixture and extracted 3 times with 20 ml of diethyl ether. The extracts are washed with 20 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate. 12.12 g of alpha-(p-toluenesulfonyloxy)-p-methoxypropiophenone dimethyl acetal are obtained as a light yellow oil. The yield is 80%.

IC (neat): 1600, 1510, 1350, 1245, 1170, 1090, 1055, 1035, 905 cm ^-1 .

NMR (CDCl ₃ ): delta 1.07 (3H, d, J = 7 Hz), 2.40 (3H, s), 3.07 (3H, s), 3.12 (3H, s), 3.75 (3H, s), 4.92 (1H, q, J = 7 Hz), 6.7 to 7.0 (2H, m), 7.1 to 7.4 (4H, m),

7.73 (2H, d, J=8 Hz).

Example 11

By a similar procedure as in Example 1, alpha-bromo-p-(tert-butyl)isovalerophenone is produced from p-(tert-butyl)isovalerophenone as a colorless liquid. The yield is 72%.

Boiling point: 128 to 140 °C/133 Pa. IR (clean): 2,960.1 680, 1,600 -1 cm NMR (CDCl 3 ) : delta 1, 00 (3H, d, J = 7 Hz) , 1.20 (3H, d, J = 7 Hz) , 1.35 (9H, s), 2.2 to 2.7 (1H, = 10 Hz) m) , 4.90 (1H, d, , J = 9 Hz), 7.47 (2H, d, J = 10 Hz), 7.90 (2H, d, Analysis of ^{C15H21OBr ​ ​} read: 60.61% C, 7.12% H, 26.89 % Br, found: 60.71% C, 7.11% H, 26.58 % Br.

Example 12

1.62 g of sodium methoxide was dissolved in 20 ml of anhydrous methanol and the solution was stirred at room temperature under argon. To the resulting solution was added 20 ml of a solution of 2.64 g of alpha-bromo-p-(tert-butyl)isovalerophenone in anhydrous methanol over 15 minutes and the mixture was stirred at room temperature for 18 hours.

By the usual work-up as described in Example 2, 2.44 g of alpha-hydroxy-p-(tert-butyl)isovalerophenone dimethyl acetal are obtained in the form of a light yellow oil. The yield is 98%.

IR (pure): 2950, 1110, 1040 cm ^-1 .

NMR (CDCl ₃ ): delta 0.70 (3H, d, J = 7 Hz), 0.90 (3H, d, J = 7 Hz), 2.32 (9H, s), 1.0 to

1.6 (1H, m), 2.45 (1H, broad s), 3.22 (3H, s), 3.25 (3H, s), 3.67 (1H, d, J = = 6 Hz) , 7.33 (4H, s) .

Example 13

1.90 g of methanesulfonyl chloride is dissolved in 5 ml of anhydrous pyridine and the solution is stirred at room temperature. 5 ml of a solution of 2.34 g of alpha-hydroxy-p-(tert-butyl)isovalerophenone dimethyl acetal in anhydrous pyridine is added dropwise to the solution over 10 minutes and the mixture is stirred at this temperature for a further 24 hours. By the usual work-up and separation of the product as described in Example 7, 1.63 g of alpha-(methanesulfonyloxy)-p-(tert-butyl)isovalerophenone dimethyl acetal is obtained as a colourless oil (this compound crystallizes on standing at room temperature). The yield is 55%.

Melting point: 80 to 86 °C.

IR (neat): 2960, 1357, 1176, 1060, 955 cm ¹ NMR (CDC1 ₃ ): delta 0.70 (3H, d, J = 7 Hz), 0.90 (3H, d, J = 7 Hz), 1.32 (9H, s), 1.4 to

1.9 (1H, m), 3.17 (3H, s), 3.20 (3H, s), 3.26 (3H, s), 4.76 (1H, d, J = 4 Hz), 7.37 (4H, s).

Analysis for ^c i8 ^H 30°5 ^K: calculated: 60.30% C, 8.44% H, 8.95% S, found: 60.07% C, 8.33% H, 9.07% S.

Example 14

To a mixture of 7.12 g of alpha-acetoxyacetophenone, 7.44 g of ethylene glycol and 0.200 g of p-toluenesulfonic acid monohydrate, 100 ml of benzene is added and the mixture is heated to reflux. The resulting water is removed using a Dean-Stark trap attached to the reaction vessel.

After 21 hours of refluxing, 4.00 g of ethylene glycol are added. The mixture is further refluxed for 6 hours. The water formed is distilled off. After cooling, 30 ml of saturated aqueous sodium bicarbonate solution and 20 ml of water are gradually added to the mixture and the mixture is extracted twice with 30 ml of diethyl ether. The extracts are washed with 10 ml of water, dried with anhydrous magnesium sulfate and evaporated under reduced pressure. 7.874 g of a residue are obtained, which according to NMR and gas-liquid chromatography consists of a mixture of alpha-hydroxyacetophenone ethylene acetate and alpha-acetoxyacetophenone ethylene acetal. The mixture is dissolved in 20 ml of methanol and 0.300 g of potassium carbonate is added. The mixture is stirred at room temperature for 4 hours, 200 ml of water is added, and the colorless crystalline precipitate is filtered and dried overnight under reduced pressure with potassium hydroxide. 4.79 g of alpha-hydroxyacetophenone ethylene acetal is obtained. The yield is 67%;

NMR (CDCl 3 ): delta 2.10 (1H, broad s), 3.70 (2H, broad s), 3.7 to 4.0 (2H, m), 4.0 to 4.2 (2H, m), 7.2' to 7.6 (5H, m).

Example 15

To 0.900 g of alpha-hydroxyacetophenone ethylene acetal was added 5 ml of pyridine and the mixture was stirred under ice-cooling. To the mixture was added 1.08 g of p-toluenesulfonyl chloride, stirred for 2 hours under ice-cooling and then for 1 hour at room temperature. The reaction mixture was cooled with ice, 10 ml of water was added and the mixture was stirred for a further 1 hour and extracted 3 times with 20 ml of diethyl ether. The extracts were washed 2 times with 10 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. 1.584 g of a crystalline residue was obtained, which was washed with a small amount of hexane, whereby 1.330 g of alpha-(p-toluenesulfonyloxy)acetophenone ethylene acetal was obtained in the form of colorless crystals. The yield was 80%.

NMR (CDCl ₃ ): delta 2.40 (3H, s), 3.7 to 3.9 (2H, m) , 3.9 to 4.1 (2H, m), 4.11 (2H, s) ,

7.1 to 7.5 (5H, m), 7.55 (2H, d, J = 8 Hz).

Example 16

Using a similar procedure as in Example 15, alpha-(p-bromobenzenesulfonyloxy)acetophenone ethylene acetal is obtained from alpha-hydroxyacetophenone ethylene acetal in the form of colorless crystals. The yield is 86%.

NMR (CDCl ₃ ): delta 3.7 to 3.9 (2H, m), 3.9 to 4.1 (2H, m), 4.16 (2H, s), 7.2 to 7.5 (5H, m), 7.63 (4H, s).

Example 17

0.46 g of sodium metal is dissolved in 10 ml of anhydrous methanol and the solution is stirred at room temperature. 10 ml of a solution of 2.19 g of 1-(2-thienyl)-2-bromo-1-oxopropane in anhydrous methanol is added dropwise to the solution over 10 minutes and the mixture is stirred for a further 3.5 hours at room temperature. By the usual work-up as in Example 2, 1.900 g of 1-(2-thienyl)-2-hydroxy-1-oxopropane dimethyl acetal is obtained in the form of a colourless oil. The yield is 94%.

IC (neat): 3450, 1110, 1055, 980, 855, 710 cm ¹ .

NMR (CDCl ₃ ): delta 1.05 (3H, d, J = 7 Hz), 2.54 (1H, broad s), 3.26 (3H, s), 3.30 (3H, s),

4.16 (1H, wide q, J = 7 Hz), 6.9 to 7.2 (2H, m), 7.2 to 7.4 (1H, m).

Example 18

0.606 g of 1-(2-thienyl)-2-hydroxy-1-oxopropane dimethyl acetal was dissolved in 5 ml of pyridine and the solution was stirred under ice-cooling. 0.30 ml of methanesulfonyl chloride was added to the solution over 1 minute and the mixture was stirred under ice-cooling for 5 minutes and then at room temperature for 5 hours.

30 ml of water are added to the mixture and stirred for 30 minutes at room temperature. Then it is extracted 3 times with diethyl ether. The extracts are washed 2 times with 10 ml of water, dried with anhydrous magnesium sulfate and anhydrous potassium carbonate and evaporated under reduced pressure. The residue is purified by column chromatography (Florisil, methylene chloride). 0.788 g of 1-(2-thienyl)-2-(ethanesulfonyloxy)-1-oxopropane dimethyl acetal is obtained in the form of a colorless oil. The yield is 94%.

IR (clean): 1,360, 1,180, 1,120, 1,055, 990, 975, 930, 905, 855, 810, 715, 540, 525 cm" ¹ .

NMR (CDCl ₃ ): delta 1.27 (3H, d, J = 7 Hz), 3.09 (3H, s), 3.27 (6H, s), 5.02 (1H, q, J = 7 Hz),

6.9 to 7.1 (2H, m), 7.2 to 7.4 (1H, m).

Analysis for calculated: 42.84% C, 5.75% H, 22.87% S, found: 42.64% C, 5.64% H, 22.90% S.

Example 19

In 10 ml of anhydrous pyridine, 2.01 g of benzenesulfonyl chloride are dissolved and the solution is stirred at room temperature. To the solution, 10 ml of a solution of 1.93 g of alpha-hydroxy-p-isobutylpropiophenone dimethyl acetal in anhydrous pyridine is added dropwise over 15 minutes and the mixture is stirred for 72 hours.» By a similar treatment as in Example 3, 2.62 g of alpha-(benzenesulfonyloxy)-p-isobutylpropiophenone dimethyl acetal are obtained in the form of colorless crystals. The yield is 88%.

Melting point: 79 to 82 °C.

iC (KBr) : 2 950, 1 362 , 1,195, 1,097, 1,043, 990, 921, 813, 594 cm ^-1 . NMR (CDC1 ₃ ): : delta 0.86 I (6H, d. J = 7 Hz), 1.08 (3H, d, J = 7 Hz), 1.6 until 2.1 (1H, m), 2.41 (2H, d, J = 7 Hz), 3.02 (3H, s), 3.10 (3H, s), 4.94 (1H, q, J « 7 Hz), 7.04 (2H, d, J = 9 Hz), 7.19 (2H, d, J = 9 Hz), 7.36 to 7 , 70 (3H, m), 7.84 to 8.02 (2H, m) .

Example 20

In 10 ml of anhydrous pyridine, 1.91 g of p-toluenesulfonyl chloride is dissolved and the solution is stirred at room temperature. Over 10 minutes, 10 ml of a solution of 1.13 g of alpha-hydroxypropiophenone diethyl acetal in anhydrous pyridine is added dropwise to the solution and the mixture is stirred for 72 hours. By conventional work-up and purification by column chromatography, 1.16 g of alpha-(p-toluenesulfonyloxy)propiophenone diethyl acetal is obtained as a colorless oil. The yield is 85%.

IR (pure): 2,980, 1,360, 1,192, 1,178, 1,087, 1,055, 1,042, 920 cm ¹ .

NMR (CDCl ₃ ): delta 0.8 to 1.3 (9H, m), 2.38 (3H, s), 3.1 to 3.6 (4H, ra), 4.89 (1H, q, J = = 7 Hz), 7.1 to 7.5 (7H, m), 7.80 (2H, d, J = 9 Hz).

Analysis for ^C 20 ^řI 26°5 ^S:

calculated: 63.46% C, 6.93% H, 8.47% S found: 63.54 l C, 6.90% H, 8.35% S Example 21

By a similar procedure to Example 17, 1-(4-methoxyphenyl)-2-bromo-1-oxopropane was used to prepare 1-(4-methoxyphenyl)-2-hydroxy-1-oxopropane dimethyl acetal as a pale yellow oil. The crude product was used in the reaction in Example 22 without further purification.

Example 22

By a similar procedure to Example 7, 1-(4-methoxyphenyl)-2-hydroxy-1-oxopropane dimethyl acetal (obtained in Example 21) was used to prepare 1-(4-methoxyphenyl)-2-methanesulfonyloxy-1-oxopropane dimethyl acetal as a light yellow oil. The yield was 80.1% (calculated on 1-(4-methoxyphenyl)-2-bromo-1-oxopropane).

IR (pure): 2,935, 1,615, 1,517, 1,358, 1,257, 1,176, 1,100, 1,065, 145, 915 cm ¹ .

NMR (CDCl ₃ ): delta 1.18 (3H, d, J = 6 Hz) , 3.09 (3H, s), 3.21 (3H, s), 3.28 (3H, s) 3.80 (3H, s), 4.97 (1H, q, J = 6 Hz), 6.87 (2H, d, J = 9 Hz), 7.37 (2H, d, J = 9 Hz).

Example 23

In a similar manner to Example 20, 1-(2-thienyl)-2-hydroxy-1-oxopropane dimethyl acetal was used to prepare 1-(2-thienyl)-2-(p-toluenesulfonyloxy)-1-oxopropane dimethyl acetal as a colorless oil in 64% yield.

IR (pure): 1,360, 1,190, 1,180, 1,060, 985, 925, 905, 820, 790, 710, 665, 565 cm ¹ .

NMR (CDCl ₃ ): delta 1.19 (3H, d, J = 7 Hz), 2.40 (3H, s), 3.08 (3H, s), 3.14 (3H, s), 4.98 (1H, q, J = 7 Hz), 6.94 (2H, d, J = 3 Hz), 7.2 to 7.4 (3H, m), 7.80 (2H, d, J = = 8 Hz).

Example 24

In a similar manner to Example 20, 1-(2-thienyl)-2-hydroxy-1-oxopropane dimethyl acetal and benzenesulfonyl chloride were used to prepare 1-(2-thienyl)-2-benzenesulfonyloxy-1-oxopropane dimethyl acetal as a colorless oil in 83% yield.

IR (clean) : 1,360, 1,190, 1,060, 980, 925, 900, 590, 555 cm 1. NMR (CDCl ₃ ): delta 1.20 (3H, d, J = 7 Hz), 3.08 (3H, s), 3.14 (3H, s), 5.01 (1H, q, J - 7 6.8 to 7.1 (2H, m), 7.2 to 7.4 (1H, m) , 7.4 to 7.7 (3H, m) 7.9 to 8.1 (2H, ni) Exhibit 1 and 25 At 30 ml of anhydrous ethanol is dissolved 1.30 g (56.5 nunol) of sodium metal and the mixture is mixes at room temperature. Within 15 minutes to solution drop 20 ml of solution 5.33 g

(0.025 mol) of alpha-bromopropiophenone in anhydrous ethanol and the mixture is stirred for a further 40 minutes at room temperature. Then 100 ml of water is added and the mixture is extracted twice with 60 ml of diethyl ether. The extracts are washed with water, dried with anhydrous magnesium sulphate and anhydrous potassium carbonate and evaporated under reduced pressure. The residue is dissolved in 30 ml of anhydrous ethanol containing a catalytic amount of sodium metal dissolved therein and the solution is stirred for 2 days at room temperature. By the usual work-up as in Example 2, 4.497 g of 1-phenyl-2-hydroxy-1-oxopropane diethyl acetal are obtained in the form of a colourless oil. The yield is 80.2%.

IC (neat): 2960, 1452, 1120, 1092, 1057, 1040, 772, 709 cm” ¹ .

NMR (CDCl 3 ): delta 0.94 (3H, d, J = 6 Hz), 1.05 to 1.40 (6H, m), 2.61 (1H, broad s), 3.22 to 3.83 (4H, m), 4.05 (1H, q, J = 6 Hz), 7.1 to 7.7 (5H, m).

Example 26

In 20 ml of carbon disulfide, 3.33 g of acetanilide and 4.0 ml (5.2 g) of alpha-chloropropionyl chloride are stirred at room temperature. Then, 7.0 g of aluminum chloride in the form of a fine powder are added to the solution over the course of 2 minutes. The mixture is stirred at room temperature for 25 minutes and refluxed with stirring for 50 minutes. After cooling, the reaction mixture is separated into 2 layers. The upper layer is removed by decantation and the lower layer, which is black and tarry, is poured onto a mixture of water and ice. The precipitated crystals are filtered off. Recrystallization from ethanol yields 1.860 g of 1-(4-acetylaminophenyl)-2-chloro-1-oxopropane in the form of colorless crystals. The upper layer of the reaction mixture, the filtrate formed during the collection of crystals and the mother liquor from the recrystallization are combined and extracted 3 times with 50 ml of methylene chloride. The extracts are washed with 50 ml of water, dried with anhydrous magnesium sulfate and evaporated under reduced pressure. Recrystallization of the residue from ethanol gives 1.434 g of 1-(4-acetylaminophenyl)-2-chloro-1-oxopropane. The mother liquors are evaporated under reduced pressure and the residue is purified by column chromatography (silica gel, methylene chloride and ether). Recrystallization from methanol further gives 0.868 g of the product mentioned above. The total amount of product is therefore 4.162 g and the total yield is 75%. The substance forms colorless crystals.

Melting point: 123 to 125 °C (from ethanol).

XC (KBr): 1690, 1675, 1595, 1540, 1415, 1320, 1360, 1180, 965, 860, 665 cm ^-1 .

NMR (CDCl ₃ ): delta 1.70 (3H, <5, J = 7 Hz) 2.18 (3H, s), 5.18 (1H, q, J = 7 Hz), 7.63 (2H, d, J = 9 Hz), 7.95 (2H, d, J = 9 Hz), 7.8 to 8.1 (1H, broad s).

Analysis for C^^H^ ₂ ^ε 1 ^ΝΟ 2 ^: calculated: 58.54% C, 5.36% H, 15.71% Cl, 6.21% N, found: 58.59% C, 5.40% H, 15.63% Cl, 6.23% N.

Example 27

By a similar procedure to Example 17, 1-(4-acetylaminophenyl)-2-chloro-1-oxopropane was prepared from 1-(4-acetylaminophenyl)-2-hydroxy-1-oxopropane dimethyl acetal as a glassy substance. The crude product was used without purification in the reaction of Example 28.

NMR (CDCl ₃ ): delta 0.95 (3H, d, J = 7 Hz) 2.14 (3H, s), 2.94 (1H, broad s), 3.21 (3H, s) ,

3.33 (3H, s), 4.10 (1H, q, J = 7 Hz), 7.37 (2H, d, J = 8 Hz), 7.51 (2H, d, J =

Hz), 8.93 (1H, broad s).

Example 28

All of the dimethyl acetal of 1-(4-acetylaminophenyl)-2-hydroxy-1-oxopropane obtained in the example was dissolved in 5 ml of pyridine and 0.60 ml (0.89 g) of methanesulfonyl chloride was added. The mixture was stirred at room temperature for 5 hours, the reaction mixture was cooled with ice and 30 ml of water was added. The temperature was allowed to return to room temperature, the mixture was stirred for 10 minutes and then extracted 4 times with 20 ml of ethyl acetate. The extracts were dried by successive addition of anhydrous sodium sulfate and anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Florisil, methylene chloride and diethyl ether) to give 1.537 g of dimethyl acetal of 1-(4-acetylaminophenyl)-2-methanesulfonyloxy-1-oxopropane as a colorless glassy substance. The yield is 93% (calculated on 1-(4-acetylaminophenyl)-2-chloro-1-oxopropane).

IR (KBr): 1,675, 1,610, 1,540, 1,350, 1,175, 915, 525 cm ^-1 .

NMR (CDCl1): delta 1.14 (3H, d, J = 7 Hz), 2.52 (3H, s), 3.08 (3H, s), 3.18 (3H, s), 3.24 (3H, s), 4.94 (1H, q, J = 7 Hz), 7.36 (2H, d, J = 9 Hz), 7.54 (2H, d, J = 9 Hz). 9 Hz), 8.52 (1H, wide s).

Example 29

In the same manner as in Example 17, 1-(4-fluorophenyl)-2-bromo-1-oxopropane was used to prepare 1-(4-fluorophenyl)-2-hydroxy-1-oxopropane dimethyl acetal, which formed a light yellow oil. This product was used in the reactions of Examples 25 and 31 without purification.

IR (pure): 2,975, 2,937, 1,610, 1,512, 1,230, 1,159, 1,105, 1,053, 982, 839 cm ¹ .

NMR (CDCl1): delta 0.93 (3H, d, J = 6 Hz), 2.53 (1H, broad s), 3.23 (3H, s), 3.33 (3H, s), 4.08 (1H, broad q, J = 6 Hz), -6.83 to 7.18 (2H, m), 7.32 to 7.60 (2H, m).

Example 30

In the same manner as in Example 7, 1-(4-fluorophenyl)-2-hydroxy-1-oxopropane dimethyl acetal (obtained in Example 29) was used to prepare 1-(4-fluorophenyl)-2-methanesulfonyloxy-1-oxopropane dimethyl acetal as a colorless oil. The yield was 82.3% (calculated on 1-(4-fluorophenyl)-2-bromo-1-oxopropane).

IC (pure): 2,940, 1,610, 1,512, 1,359, 1,228, 1,180, 1,160, 1,098, 1,067, 1,045, 972,

918 cm' ³ '.

NMR (CDCl ₃ ): delta 1.15 (3H, d, J = 6 Hz), 3.06 (3H, s), 3.21 (3H, s), 3.24 (3H, s), 4.96 (1H, q, J = 6 Hz), 6.88 to 7.16 (2H, m), 7.32 to 7.58 (2H, m).

Example 31

In the same manner as in Example 20, 1-(4-fluorophenyl)-2-hydroxy-1-oxopropane dimethyl acetal (obtained in Example 29) was used to prepare 1-(4-fluorophenyl)-2-(p-toluenesulfonyloxy)-1-oxopropane dimethyl acetal in the form of colorless crystals with a melting point of 96 to 99° C. The yield was 76.2% (calculated on 1-(4-fluorophenyl)-2-bromo-1-oxopropane).

Melting point: 101 °C (from methanol).

IC (KBr): 2,948, 1,605, 1,510, 1,360, 1,346, 1,192, 1,181, 1,090, 1,053, 932, 918, 820, 786, 670, 561 cm ^-1 .

NMR (CDCl ₃ ): delta 1.05 (3H, d, J = 6 Hz), 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s), 4.93 (1H, q, J = 6 Hz), 6.82 to 7.08 (2H, m), 7.16 to 7.46 (4H, m), 7.73 (2H, d,

J = 8 Hz).

Analysis for ^c ^g ^H 2] ^FO 3 ^S: calculated: 58.68% C, 5.75 i H, found: 58.98 i C, 5.96 i H.

Example 32

In 60 ml of anhydrous dioxane, 8.57 g of 1-(6-methoxy-2-naphthyl)-1-oxopropane (U.S. Patent No. 2,683,738) was dissolved and the solution was stirred at room temperature. 13.57 g of pyridinium hydrobromide perbromide was added to the solution and then stirred for another hour. 200 ml of

3% aqueous sodium bisulfite solution and after 3 hours of stirring at room temperature, the precipitated crystals are filtered off, washed with water and dried under reduced pressure with potassium hydroxide. 11.66 g of 1-(6-methoxy-2-naphthyl)-2-bromo-1-oxopropane are obtained in the form of light yellow crystals and a melting point of 73-75 °C. The yield is 99%.

Melting point: 68 to 69 °C (from benzene).

NMR (CDCip: delta 1.90 (3H, d, J = 7 Hz), 3.85 (3H, s), 5.36 (1H, q, J = 7 Hz), 6.9 to 7.3 (2H, m), 7.5 to 8.1 (3H, m), 8.38 (1H, broad s).

Analysis for C^^H^^BrO^:

calculated: 57.35% C, 4.47% H, 27.26% Br, found: 57.27% C, 4.66% H, 27.23% Br.

Example 33

By a similar procedure as in Example 2, 1-(6-methoxy-2-naphthyl)-2-bromo-1-oxopropane is used to produce 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-oxopropane dimethyl acetal in the form of a colorless oil. The yield is 100%. The product crystallizes after purification by column chromatography (Florisil, methylene chloride) and after standing at room temperature. The substance forms colorless crystals.

Melting point: 56 to 59 °C.

IC (KBr) : 3500, 1637,. 1610, 1488, 1276, 1215, 1175, 1118, 1106, 1040, 859 cm ^-1 .

NMR (CDCl1): delta 0.97 (3H, d, J = 7 Hz), 2.48 (1H, broad s), 3.20 (3H, s), 3.36 (3H, s),

3.82 (3H, s), 4.14 (1H, q, J = 7 Hz) 7.00 to 7.24 (2H, m), 7.40 to 7.98 (4H, m).

Analysis for ^c i6 ^H 20°4 ^: calculated: 69.54% C, 7.30 % H found: 69.25% C, 7.28 % H Example 34

By a similar procedure to Example 7, 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-oxopropane dimethyl acetal was prepared from 1-(6-methoxy-2-naphthyl)-2-methanesulfonyloxy-1-oxopropane dimethyl acetal in the form of a colorless oil. The yield was 84%.

IC (neat): 1640, 1615, 1492, 1360, 1280, 1182, 901, 820 cm ^-1 .

NMR (CDCl1) delta 1.19 (3H, d, (1H, q, J = 7 Hz),

J = 7 Hz) , 3.09 (3H, s) , 3.22 (3H, s), 3.31 (3H, s), 3.87 (3H, s), 5.05 7.04 to 7.24 (2H, m), 7.42 to 7.94 (4H, m).

Analysis for calculated found:

57.61% C, 6.26% H, 57.21% C, 6.02% H,

Example

9.05% S, 8.85% S.

350 mg of sodium metal was dissolved in 40 ml of anhydrous methanol and the solution was stirred at room temperature. 2.93 g of 1-(6-methoxy-2-naphthyl)-2-bromo-1-oxopropane was added to the solution and then stirred for 24 hours. The mixture was mixed with 50 ml of water and then extracted 4 times with 15 ml of methylene chloride each time. The extract was dried with anhydrous magnesium sulfate and anhydrous potassium carbonate and evaporated under reduced pressure. 2.845 g of crude product - dimethyl acetal of l-(6-methoxy-2-naphthyl)-2-hydroxy-1-oxopropane was obtained; 1.11 g of crude product was dissolved in 3 ml of anhydrous pyridine and then stirred at room temperature. 993 mg of D-10-camphorsulfonyl chloride was added to the solution and the mixture was stirred for 40 minutes. 20 ml of water was added to the mixture and then extracted 3 times with 10 ml of methylene chloride. The extract was dried by successive addition of anhydrous magnesium sulfate and anhydrous potassium carbonate and then evaporated under reduced pressure. The remaining oil was purified by column chromatography (Florisil, methylene chloride) to give 1.467 g of 1-(6-methoxy-2-naphthyl)-2-(D-10-camphorsulfonyloxy)-1-oxopropane dimethyl acetal as a colorless glass. The yield was 76.8% (calculated on 1-(6-methoxy-2-naphthyl)-2-bromo-1-oxopropane). The product is a mixture of two diastereomers in a 1:1 ratio, as determined by high-performance liquid chromatography and NMR spectrum.

1.067 g of the product thus obtained is dissolved in 4 ml of methanol and the solution is left to stand for days at a temperature of 2 to 4 °C. 355 mg of colorless crystals with a melting point of 90 to 95 °C are obtained. The crystals are further recrystallized from methanol and 220 mg of one of the diastereomers is obtained in the form of pure product.

Melting point: 102 to 105 °C.

(βν ) 25 = +32.5° (c = 1, chloroform).

ID (KBr): 2,950, 1,753, 1,634, 1,611, 1,487, 1,354, 1,273, 1,219, 1,180, 1,166, 1,068,

042, 990, 919, 899, 862, 840 cm' ¹ .

NMR (CDCl ₃ ): delta 0.87 (3H, s) , 1.12 (3H, s), 1.23 (3H, d, J = 6 Hz) , 1.3 to 2.7 (7H, m), 3.04 (1H, d, J = 15 Hz), 3.24 (3H, s), 3.35 (3H, s), 3.86 (3H, s), 3.86 (1H, d, J = 15 Hz),

5.15 (1H, q, J = 6 Hz), 7.04 to 7.26 (2H, m), 7.46 to 7.98 (4H, m).

Analysis for ^26^33^^7^ ¹ calculated: 63.78% C, 6.79% H, 6.55% S, found: 63.66% C, 7.06% H, 6.57% S.

The second diastereomer is separated from the mixture as a colorless oil by high-performance liquid chromatography.

chromatography (column: Microporasil, column size: 7.8 mm x 30 cm, developing solvent- lo: a mixture of hexane and ethyl acetate in a ratio of 9:1). (Of)2 ⁵ = +4.2° (c = 0.143, chloroform) • ID (KBr): 2,950, 1,750, 1,631, 1,608, 1,485, 1,352, 1,271 , 1,216, 1,172, 1,062, 1 040, 985, 914, 895, 855, 810 cm ¹ . NMR (CDCl ₃ ): delta 0.91 (3H, s), 1.14 (3H, s), 1.26 (3H, d, J = 6 Hz), 1.3 to 2.7 (7H, m), 3.29 (1H, d, J = 15 Hz), 3.30 (3H, s), 3.42 (3H, s), 3.74 (1H, d, J = = 15 Hz) ,

3.96 (3H, s), 5.20 (1H, q, J = 6 Hz), 7.10 to 7.30 (2H, m), 7.50 to 8.02 (4H, m)

Example 36

In a similar manner to Example 17, 1-(4-chlorophenyl)-2-bromo-1-oxopropane was used to prepare 1-(4-chlorophenyl)-2-hydroxy-1-oxopropane dimethyl acetal as a colorless oil. This product was used in the reaction of Example 37 without further purification.

IR (pure): 3,450, 2,975, 2,930, 1,600, 1,492, 1,398, 1,108, 1,095, 1,052, 1,016, 980, 829, 743 cm 1.

Example 37

In the same manner as in Example 20, 1-(4-chlorophenyl)-2-hydroxy-1-oxopropane dimethyl acetal obtained in Example 36 was used to produce 1-(4-chlorophenyl)-2-(p-toluenesulfonyloxy)-1-oxopropane dimethyl acetal in the form of white crystals with a melting point of 76-77° C. The yield was 86% (calculated on 1-(4-chlorophenyl)-2-bromo-1-oxopropane).

Melting point: 78-79°C (from methanol).

iC (KBr): 2945, 1601, 1493, 1364, 1347, 1195, 1188, 1094, 1057, 1110, 936, 919,

822, 789, 669, 565 cm" ¹ .

NMR (CDCl ₃ ): delta 1.05 (3H, d, J = 6 Hz) 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s), 4.93 (1H, q, J = 6 Hz), 7.25 (4H, s), 7.27 (2H, d, J = 8 Hz), 7.76 (2H, d, J = 8 Hz). 8 Hz).

Analysis for ^c ig ^H 21 ^S °3 ^G ^ ^: calculated: 56.17% C, 5.50% H, 9.21% Cl, 8.33% S, found: 56.22% C, 5.48% H, 9.13% Cl, 8.32% S.

Example 38

In the same manner as in Example 26, 1-(4-)-1-oxo-4-isoindolinyl(phenyl)-2-chloro-1-oxopropane was prepared from 2-phenyl-1-isoindoline and alpha-chloropropionyl chloride in the form of colorless crystals. The yield was 89%.

Example 39

In the same manner as in Example 17, 1-(4-)-2-oxo-2-isoindolinyl(phenyl)-2-chloro-1-oxopropane is used to produce 1-(4-)1-oxo-2-isoindolinyl(phenyl)-2-hydroxy-1-oxopropane dimethyl acetal in the form of colorless crystals with a melting point of 130 to 135 °C. The yield is 83%.

IC (KBr): 3,530, 1,680, 1,515, 1,385, 1,310, 1,120, 1,045.'740 cm' ¹ .

NMR (CDCl1): delta 0.96 (3H, d, J = 7 Hz), 2.36 (1H, broad s), 3.20 (3H, s), 3.33 (3H, s), 4.10 (1H, broad q, J = 7 Hz), 4.80 (2H, s), 7.4 to 7.6 (5H, m), 7.8 to 8.0 (3H, m).

Analysis for iW calculated: 69.70 %c, 6.47% H, 4.28% N found: 69.63 %c, 6.49% H, 4.21% N Example 40

In the same manner as in Example 28, dimethyl acetal of 1-(4-)1-oxo-2-isoindolinyl(phenyl)-2-hydroxy-1-oxopropane is prepared from dimethyl acetal of 1-(4-)1-oxo-2-isoindolinyl(phenyl)-2-methanesulfonyloxy-1-oxopropane in the form of colorless crystals, the yield is 95%.

IC (KBr): 1695, 1520, 1390, 1350, 1340, 1175, 975, 910, 740 cm ¹ .

NMR (CDCl ₃ ): delta 1.20 (3H, d, J = 7 Hz), 3.11 (3H, s), 3.24 (3H, s), 3.30 (3H, s), 4.81 (2H, s), 5.00 (1H, q, J = 7 Hz), 7.4 to 7.6 (5H, m), 7.8 to 8.0 (3H, m).

Example 41

In the same manner as in Example 17, 1-(4-biphenylyl)-2-bromo-1-oxopropane is used to produce 1-(4-biphenylyl)-2-hydroxy-1-oxopropane dimethyl acetal in the form of colorless crystals with a melting point of 78.5 to 80°C. The yield is 95%.

Melting point: 78.5 to 80 °C (From ether and n-hexane).

NMR (CDCl1): delta 1.00 (3H, d, J = 7 Hz), 2.44 (1H, d, J = 3.1 Hz), 3.23 (3H, s), 3.37 (3H, s), 4.12 (1H, q, d, J = 7 Hz, 3.1 Hz), 7.2 to 7.7 and 7.55 (m and s, 9H).

IR (KBr): 1 118, 1 102, 1 045, 1 007, 979, 838, 770, 735, 695 cm' ¹ .

Analysis for calculated: 74.97 i C, 7.40 % H, found: 74.88 % C, 7.27 % H.

Example 42

In the same manner as in Example 7, 1-(4-biphenylyl)-2-methanesulfonyloxy-1-oxopropane dimethyl acetal was prepared from 1-(4-biphenylyl)-2-hydroxy-1-oxopropane dimethyl acetal in the form of a colorless oil.

IR (pure): 1,490, 1,357, 1,335, 1,177, 1,123, 1,100, 1,065, 1,045, 971, 916, 847, 811, 773, 753, 740, 702, 538, 527 cm ¹ .

NMR (CDCl1): delta 1.21 (3H, d, J = 7 Hz), 3.03 (3H, s), 3.24 (3H, s), 3.31 (3H, s), 5.01 (1H, q, J = 7 Hz) 7.1 to 7.7 (rrt), to 7.56 (s) all 9H.

Example 43

1,1-dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene was prepared from 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene by a similar procedure to that described in Example 17. This product was used without purification in the reaction described in Example 44.

IR (pure): 1,138, 1,080, 1,058, 767 cm ¹ .

Example 44

In a similar manner to Example 7, 1,1-dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene obtained in Example 43 was used to prepare 1,1-dimethoxy-2-methanesulfonyloxy-1,2,3,4-tetrahydronaphthalene as colorless crystals with a melting point of 113. to 114.5 ° C. The yield is 46.5% (calculated on 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene).

Melting point: 113-114.5 °C (from methylene chloride, diethyl ether and n-hexane).

IR (KBr): 1,361, 1,340, 1,206, 1,175, 1,141, 1,033, 1,060, 1,050, 981, 959, 949, 917, 847, 781, 768, 625, 546, 530, 510 cm ¹ .

NMR (CDCl ₃ ): delta 2.37 (2H, m), 2.9 (2H, m), 2.94 (3H, s), 2.98 (3H, s), 3.43 (3H, s),

5.27 (1H, t, J = 3 Hz), 7.17 (3H, m), 7.63 (1H, m).

Analysis for calculated: 54.53% C, 6.34% H, 11.20% S, found: 54.73% C, 6.36% H. 11.10 4 R.

Example 45

In a similar manner to Example 32, 2-bromo-1-(4-difluoromethoxyphenyl)-1-oxopropane was prepared as a colorless oil from 1-(4-difluoromethoxyphenyl)-1-oxopropane.

NMR (CDCl1): delta 1.92 (3H, d, J = 7 Hz), 5.23 (1H, q, J = 7 Hz), 6.58 (1H, t, J = 72 Hz), 7.15 (2H, d, J = 9 Hz), 8.00 (2H, d, J = 9 Hz).

Example 46

In a similar manner to Example 17, 1-(4-difluoromethoxyphenyl)-2-hydroxy-1-oxopropane dimethyl acetal was prepared from 2-bromo-1-(4-difluoromethoxyphenyl)-1-oxopropane as a colorless oil.

IC (neat): 3600 to 3200, 1515, 1385, 1230, 1130, 1050, 840 cm ^-1 .

NMR (CDCl ₃ ): delta 0.95 (3H, d, J = 7 Hz), 2.37 (1H, d, J = 3 Hz), 3.23 (3H, s), 3.33 (3H, s), 4.10 (1H, dq, J = 3 and 7 Hz), 6.52 (1H, t, J = 74 Hz), 7.10 (2H, d,

J = 9 Hz), 7.49 (2H, d, J = 9 Hz).

Example 47

In a similar manner to Example 7, 1-(4-difluoromethoxyphenyl)-2-hydroxy-1-oxopropane dimethyl acetal obtained in Example 46 was used to prepare 1-(4-difluoromethoxyphenyl)-2-methanesulfonyloxy-1-oxopropane dimethyl acetal as a colorless oil. The yield was 55% (calculated on 1-(4-difluoromethoxyphenyl)-1-oxopropane).

IC (neat): 1515, 1360, 1235, 1180, 1130, 1100, 1070, 1045, 975, 920, 540, 530 cm ¹ .

NMR (CDCl ₃ ): delta 1.18 (3H, d, J = 7 Hz), 3.09 (3H, s), 3.15 (3H, s), 3.18 (3H, s), 4.98 (1H, q, J = 7 Hz), 6.53 (1H, t, J = 74 Hz), 7.10 (2H, d, J = 9 Hz), 7.45 (2H, d, J = 9 Hz).

Example 48

In a similar manner to Example 32, 2-bromo-1-(4-difluoromethoxyphenyl)-3-methyl-1-oxobutane was prepared from 1-(4-difluoromethoxyphenyl)-3-methyl-1-oxobutane as a colorless oil.

IC (neat): 1690, 1605, 1230, 1120, 1055 cm ¹ .

NMR (CDCl1): delta 1.02 (3H, d, J = 7 Hz), 1.21 (3H, d, J = 7 Hz), 2.1 to 2.8 (1H, m), 4.85 (1H, d, J = 9 Hz), 6.60 (1H, t, J = 74 Hz), 7.18 (2H, d, J = 9 Hz) 8.03 (2H, d, J = 9 Hz).

Example 49

In a similar manner to Example 17, 1-(4-difluoromethoxyphenyl)-2-hydroxy-3-methyl-1-oxobutane dimethyl acetal was prepared from 2-bromo-1-(4-difluoromethoxyphenyl)-3-methyl-1-oxobutane in the form of a colorless oil.

IC (clean): 3,600 to 3,300, 1,515, 1,390, 1,230, 1,130, 1,050 cm" ¹ .

NMR (CDCl ₃ ): delta 0.69 (3H, d, J = 6 Hz), 0.88 (3H, d, J = 6 Hz), 1.2 to 1.7 (1H, m),

2.50 (1H, d, J = 3 Hz) 3.22 (3H, s), 3.24 (3H, s), 3.70 (1H, dq, J = 3 and 6 Hz),

6.50 (1H, t, J = 74 Hz), 7.07 (2H, d, J = 9 Hz), 7.52 (2H, d, J = 9 Hz).

Example 50

In a similar manner to Example 13, 1-(4-difluoromethoxyphenyl)-2-hydroxy-3-methyl-1-oxobutane dimethyl acetal is prepared from 1-(4-difluoromethoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-oxobutane dimethyl acetal as a colorless oil. The yield is 76% (calculated on 1-(4-difluoromethoxyphenyl) -3-methyl-1-oxobutane). This product crystallizes on standing at low temperatures. The melting point is 60-61 °C.

IR (KBr): 1,515, 1,350, 1,230, 1,180, 1,145, 1,080, 1,055, 1,035, 975 cm ¹ .

NMR (CDCl1): delta 0.67 (3H, d, J = 6 Hz), 0.91 (3H, d, J = 6 Hz), 1.4 to 1.9 (1H, m), 3.17 (3H, s), 3.19 (3H, s), 3.22 (3H, s), 4.75 (1H, d, J = 4 Hz), 6.50 (1H, t, J = = 74 Hz), 7.08 (2H, d, J = 9 Hz), 7.50 (2H, d, J = 9 Hz).

Example 51

Dissolve 230 mg of sodium metal in 3 ml of anhydrous methanol and add 2 ml of the solution

1.43 g of 2-bromo-1-(4-ethoxyphenyl)-3-methyl-1-oxobutane in anhydrous methanol. The mixture is stirred at room temperature for 1.5 hours and then at 50 °C for 45 minutes. By the usual work-up, 1.344 g of crude product, i.e. 1-(4-ethoxyphenyl)-2-hydroxy-3-methyl-1-oxobutane dimethyl acetal, is obtained, which forms a colorless oily substance without further purification. The crude product is subjected to the reaction described in Example 52.

ID (clean): 3,600 to 3,300, 1,610, 1,515, 1,485, 1,400, 1,250, 1,175, 1,115, 1,050, 990,

925, 840, 810 cm ^-1 .

NMR (CDCl1): delta 0.68 (3H, t, J = 6 Hz), 0.87 (3H, d, J = 6 Hz), 1.39 (3H, t, J = 7 Hz),

1.2 to 1.7 (1H, m), 2.50 (1H, d, J = 3 Hz), 3.22 (3H, s), 3.24 (3H, s), 3.68 (1H, d, J = 3 and 5 Hz), 4.01 (2H, q, J = 7 Hz), 6.82 (2H, d, J = 9 Hz), 7.37 (2H, d, J = 9 Hz).

Example 52

By a similar procedure to Example 13, 1-(4-ethoxyphenyl)-2-hydroxy-3-methyl-1-oxobutane dimethyl acetal obtained in Example 51 was used to prepare 1-(4-ethoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-oxobutane dimethyl acetal in the form of colorless crystals. The yield was 62% (calculated as 2-bromo-1-(4-ethoxyphenyl)-3-methyl-1-oxobutane).

Melting point: 83 to 87 °C.

IR (KBr): 1,610, 1,335, 1,260, 1,245, 1,175, 955, 850, 840 cm ^-1 .

NMR (CDCl ₃ ): delta 0.71 (3H, d, J = 6 Hz), 0.94 (3H, d, J = 6 Hz), 1.40 (3H, t, J = 7 Hz),

1.5 to 1.9 (1H, m), 3.18 (3H, s), 3.20 (3H, s), 3.24 (3H, s), 4.02 (2H, q, J = = 7 Hz), 4.57 (1H, d, J = 3 Hz), 6.85 (2H, d, J = 9 Hz), 7.37 (2H, d, J = 9 Hz).

Example 53

In the same manner as in Example 51, 2.58 g of the crude product dimethyl acetal of 1-(4-methoxyphenyl)-2-hydroxy-3-methyl-1-oxobutane was prepared from 2.71 g of 2-bromo-1-(4-methoxyphenyl)-3-methyl-1-oxobutane in the form of a colorless oil and subjected to the reaction described in Example 54 without purification.

IR (pure): 3,600 to 3,300, 1,615, 1,515, 1,255, 1,175, 1,115, 1,045, 840 cm ^-1 .

NMR (CDCl ₃ ): delta 0.70 (3H, d, J = 6 Hz), 0.87 (3H, d, J = 6 Hz),' 1.2 to 1.7 (1H, m), 2.53 (1H, broad s), 3.33 (3H, s), 3.34 (3H, s), 3.69 (1H, d, J = 5 Hz), 3.78 (3H, s), 6.83 (2H, d, J = 9 Hz), 7.40 (2H, d, J = 9 Hz).

Example 54

In 5 ml of anhydrous pyridine, 2.58 g of 1-(4-methoxyphenyl)-2-hydroxy-3-methyl-1-oxobutane dimethyl acetal obtained in Example 53 was dissolved, and the solution was stirred under ice-cooling.

2.00 g of methanesulfonic anhydride were added to the solution and the mixture was stirred for 4 hours under ice-cooling and then for 2 hours at room temperature. 20 ml of water was added to the mixture and stirred for 1 hour at room temperature and then extracted 3 times with 20 ml of diethyl ether. The extracts were washed 2 times with 5 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue was purified by column chromatography (Florisil, methylene chloride) to give 3.10 g of Γ-(4-methoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-oxobutane dimethyl acetal as a colorless oil. This compound crystallized upon standing at room temperature. The yield was 93% (calculated on 2-bromo-1-(4-methoxyphenyl)-3-methyl-1-oxobutane).

Melting point: 71.5 to 73 °C.

IR (KBr): 1,620, 1,525, 1,355, 1,260, 1,180, 1,105, 1,055, 980, 970, 960, 945, 865, 850 cm ^-1 .

NMR (CDCl1): delta 0.69 (3H, d, J = 6 Hz), 0.89 (3H, d, J = 6 Hz), 1.5 to 1.9 (1H, m), 3.14 (3H, s), 3.16 (3H, s), 3.21 (3H, s), 3.76 (3H, s), 4.72 (1H, d, J = 4 Hz),

6.82 (2H, d, J = 9 Hz), 7.36 (2H, d, J = 9 Hz).

Example 55

To a stirred suspension of 0.65 g of sodium hydride (55% in mineral oil) in 10 ml of anhydrous tetrahydrofuran was added 2.7 ml of ethylene glycol under ice-cooling. After stirring for 40 minutes at room temperature, 2.71 g of 2-bromo-1-(4-methoxyphenyl)-3-methyl-1-oxobutane was added to the reaction mixture and the mixture was stirred for 12 hours at 60°C. 50 ml of water was added to the reaction mixture and then 3 x 30 ml of methylene chloride were extracted. The extracts were washed with 10 ml of water, dried over magnesium sulfate and evaporated under reduced pressure. The oily residue was subjected to column chromatography (Florisil, methylene chloride) to give 719 mg of 2-hydroxy-1-(4-methoxyphenyl)-3-methyl-1-oxobutane ethylene acetal as a colorless oil. The yield is 29%.

IR (pure): 3,600 to 3,400, 1,620, 1,520, 1,255, 1,175, 1,040, 845 cm ^-1 .

NMR (CDCl ₃ ): delta 0.88(3H, d, J = 6 Hz), 0.90 (3H, d, J = 6 Hz), 1.2 to 1.7 (1H, m),

2.55 (1H, wide d, J = 5 Hz), 3.5 to 4.2 (5H, m), 3.77 (3H, s), 6.83 (2H, d,

J = 9 Hz), 7.36 (2H, d, J = 9 Hz).

Example 56

By a similar procedure to Example 13, 1-(4-methoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-oxobutane ethylene acetal is prepared from 2-hydroxy-1-(4-methoxyphenyl)-3-methyl-1-oxobutane ethylene acetal in the form of colorless crystals. The yield is 78%.

Melting point: 82 to 83 °C.

IR (KBr): 1 610 , 1 510 , 1 335, 1 2.50, 1 170, 1 050, 970, 940, 930, 815 cm ¹ .

NMR (CDCl ₃ ): delta 0.91 (6H, d, J = 7 Hz), 1.5 to 1.9 (1H, m), 2.99 (3H, s), 3.6 to 4.2 (4H, m), 3.75 (3H, s), 4.67 (1H, d, J = 4 Hz), 6.83 (2H, <3, J = 9 Hz), 7.34 (2H, d, J = 9 Hz).

Example 57

In the same manner as in Example 35, 1-(6-methoxy-2-naphthyl)-2-(L-10-camphorsulfonyloxy)-1-oxopropane dimethyl acetal was prepared from L-10-camphorsulfonyl chloride and 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-oxopropane dimethyl acetal as a mixture of 2 diastereomers. The mixture was recrystallized twice from methanol to give one of the diastereomers (m.p. 93-96°C, (δ)δ 32.2° (c = 0.801, chloroform)) as colorless plate-like crystals. This product fully agrees in its 1C and NMR spectral data with one of the diastereomers of dimethyl acetal 1-(6-methoxy-2-naphthyl)-2-(D-10-camphorsulfonyloxy)-1-oxopropane, which was prepared in Example 35.

The starting L-10-camphorsulfonyl chloride was prepared from commercial ammonium L-10-camphorsulfonate j (o?)^ ² = -18.4° (c = 5.3, waterjj and thionyl chloride by the procedure described by H. Sutherland and RL Shriner in J. Am. Chem. Soc., 58 , 62 (.1936). (ΟΓ)^θ = -32.3° (c = 1.36f chloroform), melting point: 58 to 64 °C.

Example 58

799 mg of 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-oxopropane dimethyl acetal was dissolved in 3 ml of anhydrous pyridine and the solution was stirred at room temperature. 833 mg of p-toluenesulfonyl chloride was added to the solution and the mixture was stirred at room temperature for 3 days. Then 30 ml of water was added and the mixture was extracted successively with 3 x 10 ml of methylene chloride. The extracts were dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue was purified by column chromatography (silica gel, methylene chloride) to give 1.019 g of 1-(6-methoxy-2-naphthyl)-2-p-toluenesulfonyloxy-1-oxopropane dimethyl acetal as a colorless oil. The yield was 81.9%.

IC (neat): 1612, 1489, 1360, 1278, 1192, 1178, 899, 560 cm ^-1 .

NMR (CDCl ₃ ): delta 1.13 (3H, d, J = 7 Hz), 2.40 <3H, s), 3.13 (3H, s), 3.21 (3H, s) 3.88 (3H, s), 5.04 (1H, q, J = 7 Hz), 7.0 to 7.9 (10H, ra).

Example 59

To a solution of 132 mg of sodium metal in 5 ml of anhydrous methanol was added 879 mg of 1-(6-methoxy-2-naphthyl)-2-bromo-1-oxopropane. The mixture was stirred at room temperature for 7 hours. Then 20 ml of water was added and the mixture was successively extracted 3 times with 10 ml of methylene chloride. 2 drops of pyridine were added to the extracts, the mixture was dried over anhydrous magnesium sulfate and then evaporated under reduced pressure to give crude dimethyl acetal of 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-oxopropane. The crude product was dissolved in 2 ml of anhydrous pyridine without purification and the solution was stirred at room temperature. Then 0.60 ml of benzenesulfonyl chloride was added to the solution and the mixture was stirred for 20 hours. 10 ml of water are added and the mixture is extracted successively with 3 x 10 ml of methylene chloride. The extracts are washed with 10 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue is purified by column chromatography (silica gel, methylene chloride) to give 1.024 g of 1-(6-methoxy-2-naphthyl)-2-benzenesulfonyloxy-1-oxopropane dimethyl acetal as a colorless oil. The product yield is 82.0% (calculated on 1-(6-methoxy-2-naphthyl)-2-bromo-1-oxopropane).

IR (pure): 1 637, 1 612, 1 488, í 456, 1 365, 1 278, 1 190, 925, 900, 761, 598 cm' ¹

NMR (CDCl ₃ ): delta 1.15 (3H, d, J = 7 Hz), 3.10 (3H, s), 3.18 (3H, s), 5.08 (1H, q, J = = 7 Hz), 7.0 to 8.1 (11H, m).

SUBJECT OF THE INVENTION

Claims (6)

SUBJECT OF THE INVENTION A process for the preparation of acetals of alpha-sulfonyloxy ketones of the general formula II OR ² OSCK-R ⁵ Λ I, “1 in which Ar stands for a) phenyl which is optionally substituted by halogen, C ^^ - alkyl, <?! _ g -alkoxy, C ₁ _G alkanoylamino, C ₁ _G-haloalkyl, phenyl or oxo-2-isoindolinyl group, naphthyl, which is optionally substituted with C 1-8 -alkoxy or c) a thienyl group, R ¹ represents a hydrogen atom or a C 1-6 -alkyl group, or Ar and R ¹ optionally form a fused ring with the carbon atom to which they are attached; R ³ and R ⁴ independently represent C 1-6 alkyl; or together represent a C 2-6 alkylene group, R is a C 1-8 -alkyl group, a phenyl group optionally substituted by a halogen atom or a C 1-8 -alkyl group, or a camphoryl group, and optionally diastereomers thereof, characterized in that they are reacted a compound of formula V 0 X Ar - Ih (V), in which X represents a halogen atom of the formula and Ar and R with an alkali metal alkoxide, R ³ , where M is an alkali metal and R is as defined above, wherein for the preparation of compounds of the formula II wherein R and R have the same meaning and Ar, R * and R $ are as defined above, the reaction of the above compound of formula V is carried out in the presence of an alcohol of the formula R ³ OH wherein R ^J is as defined above, to give a compound of formula VI GR ⁴ (VI), Where R and R have the same meaning and denote a C 1-6 -alkyl group, Ar and R are as defined above, and for the preparation of compounds of formula II wherein R ³ and R ⁴ are different and are The C 1-4 alkyl group, Ar, R and R are as defined above, the epoxy compound of formula VII formed after reaction of the above compound of formula V with said alkali metal alkoxide Ar OR ³ AND C-CH (VII), wherein Ar, are as defined above, is reacted with an alcohol of formula R OH, wherein R ⁴ is as defined above, in the presence of an alkali metal alkoxide of the general formula R ⁴ OM, wherein R ⁴ is as defined above and M is an alkali metal, to form a compound of general formula VI where R and R are different and represent C _first-alkyl, Ar and R are as ^1-4 3 4 as above, and optionally for the preparation of compounds of formula II wherein R and R 1 together represent C ₂ 5 _G-alkylene, Ar, R and R are as defined above, reacting a compound of the above formula V with an alkylene glycol of the formula HO-R-OH, where R is a C _1-6 -alkylene group, to form a compound of formula VI wherein R aa 1 R together denote _a C .- ^ alkylene, Ar and R are as defined above, and the resultant * | 3 4 compounds of the formula VI wherein Ar and R are as defined above, R and R each independently represent C ₁ _ ₄ ~ alkyl group or together represent a C ₂ _ _6-alkylene group, is reacted with a compound of formula R ⁵ - SO 2 - Hal or (R ⁵ - SO ₂ ) ₂ O, wherein R is as defined above and Hal represents a halogen atom. 2. A process according to claim 1, wherein the compounds of the formulas V, VII and VI above are used in which. Ar is 6-methoxy-2-naphthyl, 4-isobutylphenyl group, 4-C ₃ _G-alkoxyphenyl, 4-fluormethoxyfenylovou group, 2-thienyl, 4- (l-oxo-2-isoindolinyl) -phenyl, 4-biphenylyl and 4- (tert-butyl) phenyl. 3. A process according to claim 1, wherein the compound of formula VI is 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal. 4. A process according to claim 1, wherein the compounds of formula (VI) having the corresponding meanings given above for each substituent are used to form 1- (6-methoxy-2-naphthyl) -2-methanesulfonyloxy-1-oxo, propane dimethylacetal. . 5. A process according to claim 1, wherein the compounds of formula (VI) having the corresponding meanings given above for each substituent are used to give 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) dimethyl acetal. -1-oxopropane. 6. A process according to claim 1, wherein the compounds of formula (I) are used VI with the corresponding meanings given above for the individual substituents to give 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) -1-oxopropane dimethyl acetal diastereomer.