JP2022065082A - Cyclic carbonate compound and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a cyclic carbonate compound composition, and a method for producing the same.

SOLUTION: The present invention discloses a composition containing a compound (1B) and a compound (1D). A production method therefor includes the steps of: fluorinating a mixture of 2,2-dialkyl-1,3-dioxolane-4-carboaldehyde and a trimer thereof; and de-acetoniding the product in the presence of an alcohol.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to a method for producing a cyclic carbonate compound (particularly a fluorine-containing cyclic carbonate compound) and the like.

Cyclic carbonate compounds (particularly fluorine-containing cyclic carbonate compounds) are extremely important compounds as functional materials, various chemical products such as medical and agricultural chemical compounds, and intermediates thereof.
Therefore, there is always a need to provide a new method for producing a cyclic carbonate compound.

Non-Patent Document 1 describes a method for producing a fluorinated cyclic carbonate compound.

Kerouredan et al., Synthesis, 2008, 24, pp3903-3918

An object of the present invention is to provide a new method for producing a cyclic carbonate compound.

［式中、
Ｒ^Xは、水素原子、有機基を表し、
Ｘは、ハロゲン原子を表し、
Ｙは、水素原子、又はハロゲン原子を表し、及び
ｎは、１、又は２の数を表す。］
で表される化合物［本明細書中、化合物（１Ｂ）と称する場合がある。］の製造方法であって、
式（２）：

［式中、
Ｒ^Xは、水素原子、有機基を表し、
Ｘは、ハロゲン原子を表し、
Ｙは、水素原子、又はハロゲン原子を表し、及び
ｎは、１、又は２の数を表す。］
で表される化合物［本明細書中、化合物（２）と称する場合がある。］を、
ホスゲンと反応させる工程１を含む、
製造方法、
により前記課題が解決できることを見出し、本発明を完成するに至った。 As a result of diligent studies, the present inventors have determined that the formula (1B):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
Compound represented by [In the present specification, it may be referred to as compound (1B). ] Is the manufacturing method
Equation (2):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
Compound represented by [In the present specification, it may be referred to as compound (2). ]of,
Including step 1 of reacting with phosgene,
Production method,
It was found that the above-mentioned problems could be solved, and the present invention was completed.

The present invention includes the following aspects.

［式中、
Ｒ^Xは、水素原子、有機基を表し、
Ｘは、ハロゲン原子を表し、
Ｙは、水素原子、又はハロゲン原子を表し、及び
ｎは、１、又は２の数を表す。］
で表される化合物の製造方法であって、
式（２）：

［式中、
Ｒ^Xは、水素原子、有機基を表し、
Ｘは、ハロゲン原子を表し、
Ｙは、水素原子、又はハロゲン原子を表し、及び
ｎは、１、又は２の数を表す。］
で表される化合物を、
ホスゲンと反応させる工程１を含む、
製造方法。
項２．
Ｒ^Ｘは、水素原子、又は１個以上の置換基を有していてもよい炭化水素基［当該炭化水素基には、－ＮＲ^ｏ－、＝Ｎ－、－Ｎ＝、－Ｏ－、－Ｓ－、－Ｃ（＝Ｏ）Ｏ－、－ＯＣ（＝Ｏ）－、－Ｃ（＝Ｏ）－、－Ｓ（＝Ｏ）－、－Ｓ（＝Ｏ）_２－、－Ｓ（＝Ｏ）_２－ＮＲ^ｏ－、－ＮＲ^ｏ－Ｓ（＝Ｏ）_２－、－Ｓ（＝Ｏ）－、－Ｓ（＝Ｏ）－ＮＲ^ｏ－、及び－ＮＲ^ｏ－Ｓ（＝Ｏ）－（これらの式中、Ｒ^ｏは、独立して、水素原子、又は有機基である。）からなる群より選択される１個以上の部分が挿入されていてもよい。］である項１に記載の製造方法。
項３．
Ｒ^Xは、水素原子、アルキル基、又はフルオロアルキル基である項２に記載の化合物。
項４．
Ｘは、フッ素原子である項１～３のいずれか一項に記載の製造方法。
項５．
Ｙは、ハロゲン原子である項１～４のいずれか一項に記載の製造方法。
項６．
ホスゲンは、モノホスゲン、トリホスゲン、又はフルオロホスゲンである、項１～５のいずれか一項に記載の製造方法。
項７．
（１）項１中に記載されている前記式（１Ｂ）で表される化合物、及び
（２）式（１Ｄ）：

［式中、
Ｒ^１Ｄは、アルキル基を表し、及び
ｎは、１、又は２の数を表す。］
で表される化合物
を含有する組成物。
項８．
項７に記載の組成物の製造方法であって、
（Ａ）２，２－ジアルキル－１，３－ジオキソラン－４－カルボアルデヒド及びその３量体の混合物にフッ素化剤を作用させてフッ素化する工程、及び
（Ｂ）工程（Ａ）の生成物を、式：Ｒ^１Ｄ－ＯＨ（式中の記号は、前記と同意義を表す。）で表されるアルコールの存在下で、脱アセトニド化する工程を含む、
製造方法。
項９．
前記フッ素化剤が、脱酸素的フッ素化剤である項８に記載の製造方法。
項１０．
Ｒ^１Ｄが直鎖状又は分枝鎖状のＣ１－Ｃ４アルキルである項８又は９の製造方法。
項１１．
４－（ジメトキシメチル）－１，３－ジオキソラン。 Item 1.
Equation (1B):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
It is a method for producing a compound represented by
Equation (2):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
The compound represented by
Including step 1 of reacting with phosgene,
Production method.
Item 2.
^RX is a hydrocarbon atom or a hydrocarbon group which may have one or more substituents [The hydrocarbon group includes -NR ^o- , = N-, -N =, -O-,-. S-, -C (= O) O-, -OC (= O)-, -C (= O)-, -S (= O)-, -S (= O) _2- , -S (= O) ) ₂ -NR ^o- , -NR ^o -S (= O) _2- , -S (= O)-, -S (= O) -NR ^{o-, and -NR o -} S (= O)-( In these equations, ^Ro may be independently inserted with one or more moieties selected from the group consisting of hydrogen atoms or organic groups). ] The manufacturing method according to Item 1.
Item 3.
Item 2. The compound according to Item 2, wherein ^RX is a hydrogen atom, an alkyl group, or a fluoroalkyl group.
Item 4.
The production method according to any one of Items 1 to 3, wherein X is a fluorine atom.
Item 5.
Item 6. The production method according to any one of Items 1 to 4, wherein Y is a halogen atom.
Item 6.
Item 6. The production method according to any one of Items 1 to 5, wherein the phosgene is monophosgene, triphosgene, or fluorophosgene.
Item 7.
(1) The compound represented by the above formula (1B) described in Item 1 and the formula (2) (1D):

[During the ceremony,
R ^1D represents an alkyl group and n represents a number of 1 or 2. ]
A composition containing a compound represented by.
Item 8.
Item 7. The method for producing the composition according to Item 7.
(A) A step of allowing a fluorinating agent to act on a mixture of 2,2-dialkyl-1,3-dioxolane-4-carbaldehyde and its trimer to fluorinate, and (B) the product of step (A). In the presence of an alcohol represented by the formula: R ^1D -OH (the symbols in the formula represent the same meanings as described above), comprising the step of deacetonide.
Production method.
Item 9.
Item 8. The production method according to Item 8, wherein the fluorinating agent is an oxygen scavenging fluorinating agent.
Item 10.
Item 8. The method for producing item 8 or 9, wherein ^R1D is a linear or branched C1-C4 alkyl.
Item 11.
4- (Dimethoxymethyl) -1,3-dioxolane.

According to the present invention, a new cyclic carbonate compound (particularly, a fluorine-containing cyclic carbonate compound) is provided, and a method for producing the same is provided.

Terms Symbols and abbreviations herein are in the context of the present specification and can be understood in the meaning commonly used in the art to which the present invention belongs, unless otherwise specified.
In the present specification, the phrase "contains" is used with the intention of including the phrase "consisting of" and the phrase "consisting of".
Unless otherwise specified, the steps, treatments, or operations described herein can be performed at room temperature.
In the present specification, room temperature means a temperature in the range of 10 to 40 ° C.
In the present specification, the notation "Cn-Cm" (where n and m are numbers) means that the number of carbon atoms is n or more and m or less, as is usually understood by those skilled in the art. ..

Unless otherwise specified herein, examples of "halogen atoms" can include fluorine, chlorine, bromine, and iodine.

As used herein, the term "organic group" means a group containing one or more carbon atoms (or a group formed by removing one hydrogen atom from an organic compound).

An example of the "organic group" is
An alkyl group which may have one or more substituents,
An alkenyl group which may have one or more substituents,
An alkynyl group, which may have one or more substituents,
A cycloalkyl group which may have one or more substituents,
Cycloalkenyl groups, which may have one or more substituents,
A cycloalkazienyl group which may have one or more substituents,
Aryl groups, which may have one or more substituents,
An aralkyl group which may have one or more substituents,
A non-aromatic heterocyclic group which may have one or more substituents,
Heteroaryl groups, which may have one or more substituents,
Cyano group,
Aldehyde group,
R ^r O-,
R ^r CO-,
R ^r SO _2- ,
R ^r OCO- and R ^r OSO _2-
(In these equations, R ^r is independent,
An alkyl group which may have one or more substituents,
An alkenyl group which may have one or more substituents,
An alkynyl group, which may have one or more substituents,
A cycloalkyl group which may have one or more substituents,
Cycloalkenyl groups, which may have one or more substituents,
A cycloalkazienyl group which may have one or more substituents,
Aryl groups, which may have one or more substituents,
An aralkyl group which may have one or more substituents,
A non-aromatic heterocyclic group which may have one or more substituents, or a heteroaryl group which may have one or more substituents).
Can be included.

In the present specification, the "organic group" is, for example, a hydrocarbon group which may have one or more substituents [-NR ^o- , = N-, -N =, for the hydrocarbon group. -O-, -S-, -C (= O) O-, -OC (= O)-, -C (= O)-, -S (= O)-, -S (= O) _2- , -S (= O) ₂ -NR ^o- , -NR ^o -S (= O) _2- , -S (= O)-, -S (= O) -NR ^{o-, and -NR o -} S ( = ^O )-(In these equations, Ro is independently a hydrogen atom or an organic group) and one or more portions selected from the group may be inserted. ] Can be.
As is commonly understood in the art of chemistry, examples of hydrocarbon groups with heteroatoms inserted in this way can include non-aromatic heterocyclic groups and heteroaryl groups.

In the present specification, the number of carbon atoms of the "hydrocarbon group" in the "hydrocarbon group which may have one or more substituents" is, for example, 1 to 20 or 1 to 10 (eg: 1, 2). 3, 4, 5, 6, 7, 8, 9, 10).

In the present specification,
"Hydrocarbon groups which may have one or more substituents",
"Alkyl group which may have one or more substituents",
"An alkenyl group which may have one or more substituents",
"Alkynyl group which may have one or more substituents",
"Cycloalkyl group which may have one or more substituents",
"Cycloalkenyl group which may have one or more substituents",
"Cycloalkazienyl group which may have one or more substituents",
"Aryl group which may have one or more substituents" and "Aralkyl group which may have one or more substituents"
Examples of "substituents" in the above can include halogen atoms, nitro groups, cyano groups, oxo groups, thioxo groups, sulfo groups, sulfamoyl groups, sulfinamoyl groups, and sulfenamoyl groups, respectively.
The number of the substituents can be in the range of 1 to the maximum number of replaceable groups (eg: 1, 2, 3, 4, 5, 5, 6).

In the present specification, examples of the "hydrocarbon group" are an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a cycloalkazienyl group, an aryl group, an aralkyl group, and a group thereof. Can be included.

Unless otherwise specified herein, examples of "alkyl groups" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl. , Nonyl, and decyl, which are linear or branched, can include C1-C10 alkyl groups.

As used herein, a "fluoroalkyl group" is an alkyl group in which at least one hydrogen atom is substituted with a fluorine atom.
In the present specification, the number of fluorine atoms contained in the "fluoroalkyl group" is 1 or more (eg, 1 to 3, 1 to 6, 1 to 12, 1 to the maximum number that can be replaced). be able to.
The "fluoroalkyl group" includes a perfluoroalkyl group.
A "perfluoroalkyl group" is an alkyl group in which all hydrogen atoms are substituted with fluorine atoms. Specific examples of the perfluoroalkyl group include a trifluoromethyl group (CF _3- ) and a pentafluoroethyl group (C ₂ F _5- ).
In the present specification, the "fluoroalkyl group" has, for example, 1 to 20 carbon atoms, 1 to 12 carbon atoms, 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 6 carbon atoms, and 6 carbon atoms. It can be a fluoroalkyl group having 5, carbon number 4, carbon number 3, carbon number 2, or carbon number 1.
As used herein, the "fluoroalkyl group" can be a linear or branched fluoroalkyl group.
In the present specification, the "fluoroalkyl group" is specifically, for example, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group (CF _3- ), a 2,2,2-trifluoroethyl group, or a pentafluoro. Ethyl group (C ₂ F _5- ), tetrafluoropropyl group (eg HCF ₂ CF ₂ CH _2- ), hexafluoropropyl group (eg (CF ₃ ) ₂ CH-), nonafluorobutyl group, octafluoropentyl Examples include groups (eg, HCF ₂ CF ₂ CF ₂ CF ₂ CH _2- ), tridecafluorohexyl groups and the like.

Unless otherwise specified herein, examples of "alkenyl groups" are vinyl, 1-propene-.
Linear or branched chains such as 1-yl, 2-propen-1-yl, isopropenyl, 2-butene-1-yl, 4-penten-1-yl, and 5-hexene-1-yl. Can include the C2-10 alkenyl group in the form.

Unless otherwise specified herein, examples of "alkynyl groups" include ethynyl, 1-propyne-1-yl, 2-propin-1-yl, 4-pentyne-1-yl, 5-hexin-. It can include linear or branched C2-C10 alkynyl groups such as 1-yl.

Unless otherwise specified herein, examples of "cycloalkyl groups" can include C3-C7 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like.

Unless otherwise specified herein, examples of "cycloalkenyl groups" can include C3-C7 cycloalkenyl groups such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and the like.

Unless otherwise specified, examples of the "cycloalkazienyl group" in the present specification include cyclobutadienyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, cyclononadienyl. , Cyclodecadienyl and the like can include C4-C10 cycloalkazienyl groups.

In the present specification, unless otherwise specified, the "aryl group" can be monocyclic, bicyclic, tricyclic, or tetracyclic.
In the present specification, unless otherwise specified, the "aryl group" can be a C6-C18 aryl group.
Unless otherwise specified herein, examples of "aryl groups" can include phenyl, 1-naphthyl, 2-naphthyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, and 2-anthrill.

Unless otherwise specified herein, examples of "aralkyl groups" include benzyl, phenethyl, diphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 2,2-diphenylethyl, 3-phenylpropyl, 4-. Phenylbutyl, 5-phenylpentyl, 2-biphenylylmethyl, 3-biphenylylmethyl, and 4-biphenylylmethyl can be included.

In the present specification, unless otherwise specified, the "non-aromatic heterocyclic group" can be monocyclic, bicyclic, tricyclic, or tetracyclic.
Unless otherwise specified in the present specification, the "non-aromatic heterocyclic group" is, for example, 1 to 4 selected from oxygen atom, sulfur atom, and nitrogen atom in addition to a carbon atom as a ring-constituting atom. It can be a non-aromatic heterocyclic group containing a hetero atom.
Unless otherwise specified in the present specification, the "non-aromatic heterocyclic group" can be saturated or unsaturated.
Unless otherwise specified herein, examples of "non-aromatic heterocyclic groups" include tetrahydrofuryl, oxazolidinyl, imidazolinyl (eg, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl), aziridinyl (eg: 1). -Aziridinyl, 2-aziridinyl), azetidinyl (eg 1-azetidinyl, 2-azetidinyl), pyrrolidinyl (eg 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl), piperidinyl (eg 1-piperidinyl, 2-piperidinyl, 3-piperidinyl), azepanyl (eg 1-azepanyl, 2-azepanyl, 3-azepanyl, 4-azepanyl), azocanyl (eg 1-azocanyl, 2-azocanyl, 3-azocanyl, 4-azocanyl), piperazinyl (eg) : 1,4-Piperazine-1-yl, 1,4-piperazine-2-yl), diazepinyl (eg 1,4-diazepine-1-yl, 1,4-diazepine-2-yl, 1,4- Diazepine-5-yl, 1,4-diazepine-6-yl), diazocanyl (eg 1,4-diazocan-1-yl, 1,4-diazocan-2-yl, 1,4-diazocan-5-yl) , 1,4-Diazocan-6-yl, 1,5-diazocan-1-yl, 1,5-diazocan-2-yl, 1,5-diazocan-3-yl), tetrahydropyranyl (eg, tetrahydropyran) -4-yl), morpholinyl (eg 4-morpholinyl), thiomorpholinyl (eg 4-thiomorpholinyl), 2-oxazolidinyl, dihydrofuryl, dihydropyranyl, dihydroquinolyl and the like can be included.

Unless otherwise specified herein, examples of "heteroaryl groups" are monocyclic aromatic heterocyclic groups (eg, 5- or 6-membered monocyclic aromatic heterocyclic groups), and aromatic condensations. It can include heterocyclic groups (eg, 5-18 member aromatic fused heterocyclic groups).

Unless otherwise specified herein, examples of "5- or 6-membered monocyclic aromatic heterocyclic groups" include pyrrolyl (eg, 1-pyrrolyl, 2-pyrrolill, 3-pyrrolill), frills (eg, 1-pyrrolyl, 2-pyrrolill). : 2-frill, 3-frill), thienyl (eg 2-thienyl, 3-thienyl), pyrazolyl (eg 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), imidazolyl (eg 1-imidazolyl, 2- Imidazolyl, 4-imidazolyl), isooxazolyl (eg, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), oxazolyl (eg, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isothiazolyl (eg, 3-isothiazolyl, 4). -Isotiazolyl, 5-isothiazoleyl), thiazolyl (eg 2-thiazole, 4-thiazolyl, 5-thiazolyl), triazolyl (eg 1,2,3-triazole-4-yl, 1,2,4-triazole-3) -Il), oxadiazolyl (eg 1,2,4-oxadiazole-3-yl, 1,2,4-oxadiazole-5-yl), thiadiazolezolyl (eg 1,2,4-thiadiazole-3) -Il, 1,2,4-thiadiazole-5-yl), tetrazolyl, pyridyl (eg 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridadinyl (eg 3-pyridazinyl, 4-pyridazinyl), pyrimidinyl (eg 3-pyridazinyl, 4-pyridazinyl) Examples: 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), pyrazinyl and the like can be included.

Unless otherwise specified in the present specification, examples of "5- to 18-membered aromatic fused heterocyclic groups" include isoindolyl (eg, 1-isoindrill, 2-isoindrill, 3-isoindrill, 4-isoindrill, 5-isoindrill). Isoindrill, 6-isoindrill, 7-isoindrill), indrill (eg 1-indrill, 2-indrill, 3-indrill, 4-indrill, 5-indrill, 6-indrill, 7-indrill), benzo [b] flanil ( Examples: 2-benzo [b] flanyl, 3-benzo [b] flanil, 4-benzo [b] flanil, 5-benzo [b] flanyl, 6-benzo [b] flanil, 7-benzo [b] flanyl) , Benzo [c] furanyl (eg 1-benzo [c] furanyl, 4-benzo [c] furanyl, 5-benzo [c] furanyl), benzo [b] thienyl, (eg 2-benzo [b] thienyl). , 3-Benzo [b] thienyl, 4-benzo [b] thienyl, 5-benzo [b] thienyl, 6-benzo [b] thienyl, 7-benzo [b] thienyl), benzo [c] thienyl (eg) 1-benzo [c] thienyl, 4-benzo [c] thienyl, 5-benzo [c] thienyl), indazolyl (eg 1-indazolyl, 2-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6 -Indazolyl, 7-Indazolyl), Benzoimidazolyl (eg 1-benzoimidazolyl, 2-benzoimidazolyl, 4-benzoimidazolyl, 5-benzoimidazolyl), 1,2-benzoisoxazole (eg 1,2-benzoisoxazole-3) -Il, 1,2-benzoisoxazole-4-yl, 1,2-benzoisoxazole-5-yl, 1,2-benzoisoxazole-6-yl, 1,2-benzoisoxazole-7-yl ), Benzoxazolyl (eg 2-benzoxazolyl, 4-benzoxazolyl, 5-benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl), 1,2-benzo Isothiazolyl (eg 1,2-benzoisothiazole-3-3)
Il, 1,2-benzoisothiazole-4-yl, 1,2-benzoisothiazole-5-yl, 1,2-benzoisothiazole-6-yl, 1,2-benzoisothiazole-7-yl) , Benzothiazolyl (eg 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), isoquinolyl (eg 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl), quinolyl (eg) : 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 8-quinolyl), cinnolinyl (eg, 3-cinnolinyl, 4-cinnolinyl, 5-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 8-cinnolinyl) , Phtaladinyl (eg 1-phthalazinyl, 4-phthalazinyl, 5-phthalazinyl, 6-phthalazinyl, 7-phthalazinyl, 8-phthalazinyl), quinazolinyl (eg 2-quinazolinyl, 4-quinazolinyl, 5-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 8-quinazolinyl), quinoxalinyl (eg 2-quinoxalinyl, 3-quinoxalinyl, 5-quinoxalinyl, 6-quinoxalinyl, 7-quinoxalinyl, 8-quinoxalinyl), pyrazolo [1,5-a] pyridyl (eg: 2-quinoxalinyl, 8-quinoxalinyl), pyrazolo [1,5-a] pyridyl Pyrazolo [1,5-a] Pyridine-2-yl, Pyrazoro [1,5-a] Pyridine-3-yl, Pyrazoro [1,5-a] Pyridine-4-yl, Pyrazolo [1,5-a] Pyridine-5-yl, pyrazolo [1,5-a] pyridin-6-yl, pyrazolo [1,5-a] pyridin-7-yl), imidazo [1,2-a] pyridyl (eg, imidazo [1] , 2-a] Pyridine-2-yl, Imidazo [1,2-a] Pyridine-3-yl, Imidazo [1,2-a] Pyridine-5-yl, Imidazo [1,2-a] Pyridine-6 -Il, imidazo [1,2-a] pyridine-7-yl, imidazo [1,2-a] pyridine-8-yl) and the like can be included.

Unless otherwise specified in this specification.
"A non-aromatic heterocyclic group which may have one or more substituents" and "a heteroaryl group which may have one or more substituents".
Examples of each "substituent" in the above are hydrocarbon groups, halogen atoms, nitro groups, cyano groups, oxo groups, thioxo groups, sulfo groups, sulfamoyl groups, sulfinamoyl groups, which may have one or more substituents. , And sulfenamoyl groups can be included.
The number of the substituents can be in the range of 1 to the maximum number of replaceable groups (eg: 1, 2, 3, 4, 5, 5, 6).

［式中、
Ｒ^Xは、水素原子、有機基を表し、
Ｘは、ハロゲン原子を表し、
Ｙは、水素原子、又はハロゲン原子を表し、及び
ｎは、１、又は２の数を表す。］
で表される化合物（２）を、
ホスゲンと反応させる工程１を含む。 Method for Producing Compound (1B) The method for producing compound (1B) of the present invention is as follows.
Equation (2):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
The compound (2) represented by
It comprises step 1 of reacting with phosgene.

In the manufacturing method, the symbol in the formula (2) can correspond to the symbol in the formula (1B).

X is preferably a fluorine atom.

R ^X is preferably a hydrocarbon atom or a hydrocarbon group which may have one or more substituents [the hydrocarbon group includes -NR ^o- , = N-, -N =, -O. -, -S-, -C (= O) O-, -OC (= O)-, -C (= O)-, -S (= O)-, -S (= O) _2- , -S (= O) ₂ -NR ^o- , -NR ^o -S (= O) _2- , -S (= O)-, -S (= O) -NR ^{o-, and -NR o -} S (= O) )-(In these equations, ^Ro is independently a hydrogen atom or an organic group) and one or more portions selected from the group may be inserted. ].

A suitable example of the "hydrocarbon group which may have one or more substituents" is
Includes unsubstituted hydrocarbon groups.

^RX is more preferably a hydrogen atom, an alkyl group, or a fluoroalkyl group.
A suitable example of the " ^fluoroalkyl group" for the RX is a linear or branched fluoroalkyl group having 1 to 3 carbon atoms [Preferable specific examples: -CF ₃ , -CF ₂ H,-. CFH ₂ , -CH ₂ CF ₃ , -CH ₂ CF ₂ H, -CH ₂ CFH ₂ , -CF ₂ CF ₃ , -CF ₂ CF ₂ H, -CF ₂ CFH ₂ , -CFHCF ₃ , -CFHCF ₂ H, -CFHC PH ₂ , -CH (CF ₃ ) ₂ , -CH ₂ C ₂ F ₅ , -CH ₂ CF ₂ CF ₃ , -CH ₂ CF ₂ CF ₂ H, and -CF ₂ CF ₂ CF ₃ ] are included; And more preferred examples include -CH ₂ CF ₃ and -CF ₂ CF ₃ .

R ^X is more preferably a hydrogen atom, a methyl group, or a trifluoromethyl group (-C).
F ₃ ).

^RX is particularly preferably a hydrogen atom.

X is particularly preferably a fluorine atom.

Y is preferably a halogen atom.
Y is particularly preferably a fluorine atom.

n is particularly preferably 1.

Preferably,
^RX is a hydrogen atom or a methyl group.
Y is a halogen atom,
X is a halogen atom and n is a number of 1 or 2.

Preferably,
^RX is a hydrogen atom or a methyl group.
Y is a fluorine atom,
X is a fluorine atom and n is 1.

Examples of phosgene used in step 1 include monophosgene, diphosgene, triphosgene, and fluorophosgene. Of these, monophosgene, triphosgene, and fluorophosgene are preferred, and triphosgene is more preferred.

Examples of phosgene used in step 1 include precursors of monophosgene (eg, diphosgene, triphosgene).

The amount of phosgene used in step 1 is preferably in the range of 0.1 to 5 mol, more preferably in the range of 0.3 to 4 mol, with respect to 1 mol of the compound of the formula (2) in terms of phosgene. Of the above, and more preferably 0.5 to 2 mol.
In the phosgene conversion, 1 mol of triphosgene is converted into 3 mol of phosgene, and 1 mol of diphosgene is converted into 2 mol of phosgene.

The reaction of step 1 can be suitably carried out in the presence of a nucleophile.
As the nucleophile, for example, a base can be used.
The base can be an inorganic base or an organic base, preferably an organic base.
Examples of such inorganic bases include lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate.
Suitable examples of such organic bases include amines.
Examples of such catalysts include triethylamine, diisopropylethylamine, and pyridine.
The catalyst may be used alone or in combination of two or more.
The amount of the catalyst used is preferably in the range of 0.01 to 100 mol, more preferably in the range of 0.1 to 80 mol, and even more preferably in the range of 0.01 to 100 mol with respect to 1 mol of the compound of the formula (2). It can be in the range of 0.5 to 60 mol, more preferably in the range of 1 to 40 mol.

The upper limit of the reaction temperature in step 1 can be preferably −10 ° C., more preferably −20 ° C., still more preferably −30 ° C., and even more preferably −40 ° C.
The lower limit of the reaction temperature in step 1 can be preferably −200 ° C., more preferably −150 ° C., still more preferably −100 ° C., and even more preferably −80 ° C.
The reaction temperature in step 1 is preferably in the range of −200 to −10 ° C., more preferably in the range of −150 to −20 ° C., still more preferably in the range of −100 ° C. to −30 ° C., and even more preferably. , And particularly preferably in the range of −80 to −40 ° C.

The upper limit of the reaction time of step 1 can be preferably 30 minutes, more preferably 25 minutes, and even more preferably 20 minutes.
The lower limit of the reaction time of step 1 can be preferably 5 minutes, more preferably 10 minutes, and even more preferably 15 minutes.
The reaction time of step 1 can be preferably in the range of 5 to 30 minutes, more preferably in the range of 10 to 25 minutes, and even more preferably in the range of 15 to 20 minutes.

According to the production method of the present invention, the compound represented by the formula (1B) is preferably 1 to 30%, more preferably 2 to 25%, still more preferably 3 to 20%, still more preferably 4 to 4. It is obtained in yields in the range of 10%, and particularly preferably 5% to 6%.

, Step A is preferably carried out in the absence of a base or under conditions where the amount of base is small.
Specifically, the following conditions are preferable.
The upper limit of the amount of the base can be, for example, preferably 5 mol, more preferably 4 mol, and further preferably 3 mol with respect to 1 mol of the compound represented by the formula (2).
The lower limit of the amount of the base is preferably 0.01 mol, more preferably 0.1 mol, and further preferably 0.5 mol with respect to 1 mol of the compound represented by the formula (2). be able to.
The amount of the base is preferably in the range of 0.01 to 5, more preferably 0.1 to 4, and even more preferably 0.5 with respect to 1 mol of the compound represented by the formula (2). It can be in the range of ~ 3.

The reaction of step 1 can be carried out in the presence or absence of an inert gas (eg, nitrogen gas).

The reaction of step 1 can be preferably carried out in a solvent.
An example of the solvent is
(1) Hydrocarbon solvents such as hexane, heptane, cyclohexane, petroleum ether, benzene, toluene, and xylene;
It includes (2) chlorine-based solvents such as dichloromethane, dichloroethane, tetrachloroethane, and carbon tetrachloride; and (3) ether-based solvents such as diethyl ether, diisopropyl ether, THF, DME, and dioxane.
The solvent may be used alone or in combination of two or more.

If desired, the reaction of step 1 can be stopped by means such as washing the reaction product solution with water.

The compounds represented by the formula (1B) obtained in Step 1 can be simply obtained by a conventional method such as extraction, dissolution, concentration, precipitation, adsorption, or chromatography, or a combination thereof, if desired. Can be separated or purified.
If desired, the unreacted raw material can be recovered and reused.

Composition The present invention also provides a composition containing the compound represented by the formula (1B) and the compound represented by the formula (1D).

In the combination of the compound represented by the formula (1B) and the compound represented by the formula (1D) in the composition, it is represented by a common symbol in the formula (1B) and the formula (1D). The substituents and the like can be the same or different, but are preferably the same.

The composition can also be produced by simultaneously producing the compound represented by the formula (1B) and the compound represented by the formula (1D) by the production method, or is represented by the formula (1B). It can also be produced by mixing the above compound and the compound represented by the above formula (1D).

The symbol of the formula (1D), R ^1D , is preferably a linear or branched C1-C4 alkyl, and more preferably methyl.

The molar ratio of the compound represented by the formula (1B) and the compound represented by the formula (1D) is preferably in the range of 0.1: 99.9 to 99.9: 0.1.
More preferably in the range of 1:99 to 99: 1,
More preferably, in the range of 10:90 to 90:10,
It can be even more preferably in the range of 20:80 to 80:20, and particularly preferably in the range of 40:60 to 60:40.

Method for Producing Composition The composition of the present invention [that is, a composition containing the compound represented by the formula (1B) and the compound represented by the formula (1D)] is, for example,
(A) 2,2-Dialkyl-1,3-dioxolane-4-carbaldehyde [hereinafter, may be referred to as a carbide aldehyde compound. ] And the product of the step (B) step (A) in which a fluorinating agent is allowed to act on the mixture of the trimer, the formula: R ^1D -OH (the symbol in the formula is the same as above). Including the step of deacetonide formation in the presence of the alcohol represented by).
It can be manufactured by a manufacturing method.

Process (A)
Suitable examples of the carboaldehyde compound used in step (A) are:
Includes 2,2-di (C1-C4alkyl) -1,3-dioxolane-4-carbaldehyde, and more preferred examples thereof.
Includes 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde.

The molar ratio of the carboaldehyde compound and its trimer in the mixture is
Preferably in the range of 0.1: 99.9 to 99.9: 0.1,
More preferably in the range of 1:99 to 99: 1,
More preferably, in the range of 10:90 to 90:10,
It can be even more preferably in the range of 20:80 to 80:20, and particularly preferably in the range of 40:60 to 60:40.

The fluorinating agent used in the step (A) is preferably a deoxidizing fluorinating agent.
Specifically, the fluorinating agent comprises sulfur tetrafluoride (SF ₄ ), dimethylaminosulfur trifluoride, diethylaminosulfur trifluoride, morpholino sulfur trifluoride, and bis (2-methoxyethyl) aminosulfur trifluoride. It can be one or more selected from the group.

The amount of the fluorinating agent used is 1 mol of the total amount of the carboaldehyde compound and its trimer (monomer equivalent).
Preferably in the range of 1-10 mol,
It can be more preferably in the range of 1-7 mol, and even more preferably in the range of 1-5 mol.

Process (B)
Formula: The amount of alcohol used expressed by R ^1D -OH is
For 1 mol of the total amount of the carboaldehyde compound and its trimer (monomer equivalent)
Preferably 2 mol or more, and more preferably 5 mol or more,
More preferably, 10 mol or more,
Can be.
It can also be used as a reaction solvent by using the amount of the solvent.

The alcohol represented by the formula: R ^1D -OH can be used in a large excess with respect to the carboaldehyde compound and its trimer, and can also function as a reaction solvent.

R ^1D is preferably a linear or branched C1-C4 alkyl, and more preferably methyl, corresponding to the formula (1D).

The obtained composition can be isolated or purified, if desired, by a conventional method such as extraction, dissolution, concentration, precipitation, adsorption, or chromatography, or a combination thereof.
If desired, the unreacted raw material can be recovered and reused.

4- (Dimethoxymethyl) -1,3-dioxolane Among the compounds that can be produced by the production method of the present invention, 4- (dimethoxymethyl) -1,3-dioxolane is a novel compound.
That is, according to the present invention, the compound is also provided.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.
In the examples, the following abbreviations may be used.

Example 1
4- (Difluoromethyl) -1,3-dioxolane-2-one 3,3-difluoropropane-1,2-diol 14.5 g at -78 ° C, dichloromethane 300 g, pyridine 40 g, and triphosgene 15. 4 g was added and stirred for an additional 15 minutes.
After completion of the reaction, the reaction product was washed with water and purified by column chromatography.
1.08 g of 4- (difluoromethyl) -1,3-dioxolane-2-one was obtained as an oily substance.
The analysis was performed by ^{1 1} HNMR and ¹⁹ FNMR.

Example 2
Production of 4- (difluoromethyl) -1,3-dioxolane-2-one and 4- (dimethoxymethyl) -1,3-dioxolan-2-one 2,2-dimethyl-1,3-dioxolane-4-carbotype To 10 g of a mixture of aldehyde and its trimer (10: 1), 200 mL of dichloromethane was added and 22 mL of DAST was added after cooling.
After stirring, the mixture was treated with saturated aqueous sodium hydrogen carbonate solution, and extracted and concentrated with dichloromethane.
The obtained mixture was redissolved in 30 mL of methanol, and 2.4 g of p-toluenesulfonic acid / monohydrate was added under cooling and stirred.
It was treated with a small amount of triethylamine, filtered and concentrated. To the obtained mixture, 250 ml of dichloromethane was added and redissolved, 0.1 ml of DMF and 40 mL of pyridine were mixed and stirred. After nitrogen substitution, a solution of 15.4 g of triphosgene in 50 ml of dichloromethane was added dropwise at −78 ° C.
After returning the solution to room temperature and stirring, ice water was added. After the liquid separation, the organic phase was washed with 10 wt% citric acid aqueous solution three times, and then the organic layer was dried and concentrated.
The mixture was purified by column chromatography, and the desired products 4- (difluoromethyl) -1,3-dioxolane-2-one 2.4 g and 4- (dimethoxymethyl) -1,3-dioxolane-2- On 0.6 g was obtained.
The analysis was performed by ^{1 1} HNMR and ¹⁹ FNMR.

Example 3
(1) Production of 3,3-dimethoxypropane-1,2-diol Add 60 ml of water to 5.1 g of 3,3-dimethoxy-1-propene, replace with nitrogen, and then add 0.3 M permanganate at 0 ° C. 150 ml of an aqueous potassium solution was added dropwise.
The solution was returned to room temperature and stirred for 2 hours.
Then, the mixture was heated and stirred at the reflux temperature for 1 hour.
The temperature was returned to room temperature, the mixture was filtered, and 120 g of K ₂ CO ₃ was added to the filtrate. Then, it was extracted with 50 ml of ethyl acetate, and the operation was performed 5 times. The organic layer was dried and concentrated to obtain 2.0 g of the desired product.
The analysis was performed by ^{1 1} HNMR and ¹⁹ FNMR.

(2) Production of 4- (dimethoxymethyl) -1,3-dioxolane-2-one In addition to 2.0 g of 3,3-dimethoxypropane-1,2-diol, 30 ml of dichloromethane, 0.01 ml of DMF, and 3.49 g of pyridine are added. Was mixed and stirred. After nitrogen substitution, a solution of 1.74 g of triphosgene and 10 ml of dichloromethane was added dropwise at −78 ° C. The solution was returned to room temperature and ice water was added.
After the liquid separation, the organic phase was washed with 10 wt% citric acid aqueous solution three times, and then the organic layer was dried and concentrated to obtain 1.72 g of the target product.
The analysis was performed by ^{1 1} HNMR and ¹⁹ FNMR.

4- (Dimethoxymethyl) -1,3-dioxolane-2- one Of the compounds that can be produced by the production method of the present invention, 4- (dimethoxymethyl) -1,3-dioxolane- 2-one is a novel compound. ..
That is, according to the present invention, the compound is also provided.

Claims (11)

Equation (1B):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
It is a method for producing a compound represented by
Equation (2):

[During the ceremony,
^RX represents a hydrogen atom or an organic group.
X represents a halogen atom
Y represents a hydrogen atom or a halogen atom, and n represents a number of 1 or 2. ]
The compound represented by
Including step 1 of reacting with phosgene,
Production method. ^RX is a hydrogen atom or a hydrocarbon group which may have one or more substituents [The hydrocarbon group includes -NR ^o- , = N-, -N =, -O-,-. S-, -C (= O) O-, -OC (= O)-, -C (= O)-, -S (= O)-, -S (= O) _2- , -S (= O) ) ₂ -NR ^o- , -NR ^o -S (= O) _2- , -S (= O)-, -S (= O) -NR ^{o-, and -NR o -} S (= O)-( In these equations, ^Ro may be independently inserted with one or more moieties selected from the group consisting of hydrogen atoms or organic groups). ] The manufacturing method according to claim 1. The compound according to claim 2, wherein ^RX is a hydrogen atom, an alkyl group, or a fluoroalkyl group. The production method according to any one of claims 1 to 3, wherein X is a fluorine atom. The production method according to any one of claims 1 to 4, wherein Y is a halogen atom. The production method according to any one of claims 1 to 5, wherein the phosgene is monophosgene, triphosgene, or fluorophosgene. (1) The compound represented by the formula (1B) described in claim 1 and the formula (1D):

[During the ceremony,
R ^1D represents an alkyl group and n represents a number of 1 or 2. ]
A composition containing a compound represented by. The method for producing the composition according to claim 7.
(A) A step of allowing a fluorinating agent to act on a mixture of 2,2-dialkyl-1,3-dioxolane-4-carbaldehyde and its trimer to fluorinate, and (B) the product of step (A). In the presence of an alcohol represented by the formula: R ^1D -OH (the symbols in the formula represent the same meanings as described above), comprising the step of deacetonide.
Production method. The production method according to claim 8, wherein the fluorinating agent is an oxygen scavenging fluorinating agent. The method for producing claim 8 or 9, wherein ^R1D is a linear or branched C1-C4 alkyl. 4- (Dimethoxymethyl) -1,3-dioxolane.