JPS596314B2 - (E) Method for producing -2-{5-(β-substituted vinyl)-2-thienyl} fatty acid ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel novel agents having anti-inflammatory, analgesic, and hypothermic effects.
-(5-(β-monosubstituted vinyl)-2-thienyl} fatty acid ester production method.

The present inventors have intensively researched an industrially advantageous manufacturing method for the purpose of developing pharmaceuticals useful as anti-inflammatory agents. As a result, we have found that a novel compound with anti-inflammatory, analgesic, and hypothermic effects can be produced easily and with good yield. This led to the completion of a manufacturing method. That is, the present invention is applicable to general market 1) H□.

H. Y’”’ [However, X is R, □ R is a halogen atom Y is -C00R2 R2 represents a lower alkyl group.

] The ester of 5-(β-monosubstituted vinyl)-2-thienyl acetic acid is reacted with an alkali condensing agent to generate its anion, and then the anion is formed by the general formula represents a group, and z represents iodine or bromine.

] is reacted with an alkyl halide represented by the general formula 4 [provided that X. Y. R3 is the same as above] with the proviso that -2-{5-(β-monosubstituted vinyl)-2
-thienyl} fatty acid ester production method.

In the present invention, the halogen atom of R is fluorine, chlorine,
Indicates bromine and iodine. Moreover, the lower alkyl group of R2 is
A straight-chain alkyl group having 1 to 4 carbon atoms, such as methyl,
Groups such as ethyl, propyl, butyl. The starting material of the present invention (t)-5-(β-monosubstituted vinyl)-12-thienyl acetate is disclosed in Japanese Patent Application No. 50-15 filed by the present applicant.
It can be easily obtained by the usual esterification method of reacting diazomethane etc. with (t)-5-(β-substituted vinyl)-2-thienyl acetic acid, which is described in No. 6262 (Japanese Patent Application Laid-open No. 52-83360). It will be done.

In the present invention, first, at room temperature or during cooling in a nitrogen stream,
When a raw material is reacted with an alkali condensing agent in a polar or nonpolar solvent, an anion of the corresponding raw material is generated.

The production of the anion is easily confirmed by coloring, and the production time takes 30 to 1 hour. After anion 7 is produced, when an alkyl halide is reacted, α-
A monoalkylated product is obtained. The solvent used is polar solvents such as dimethylformamide, dimethyl sulfoxide, liquid ammonia, etc., and nonpolar solvents such as benzene, monoglyme, dimethoxyethane, tetrahydrofuran, etc., or a mixed solvent thereof.

In addition, alkaline condensing agents include alkali metal hydrides such as sodium hydride, potassium hydride, and lithium hydride, metal amides such as sodium amide and potassium amide, and lithium salt of diisopropylamine (produced from diisopropylamine and butyl lithium). ) etc., but are not limited to these. Obtained by the present invention (
5)-2-{5-(β-monosubstituted vinyl)-2-thienyl}
Fatty acids can also be obtained in the form of alkali metal salts such as sodium, potassium and lithium, alkaline earth metal salts such as calcium and barium, or aluminum salts by conventional methods.

Examples will be described below.

Example 1 (Section-2-Production of [5-{β-(p-chlorophenyl)vinyl}-2-thienyl]propionic acid methyl ester (t)-5-{β-(p-chlorophenyl)vinyl}-
2-thienyl acetic acid methyl ester, 1.0 r and sodium hydride (50% In mineral oil), 170T11f1 dimethoxyethane, turns red after stirring for 1 hour at room temperature in a nitrogen stream at 30 d.

Then methyl iodide, 5.0f, dimethoxyethane, 1
After dropping the solution dissolved in 0W11, the mixture was stirred for 10 minutes, poured into ice water, and extracted with ether. Dry with anhydrous magnesium sulfate. After evaporation of the solvent, the oil crystallizes. Yield: 0
．． 52f7 (yield 50%) Melting point: 62-64°C (n-hexane) Pale yellow needle crystals

Claims (1)

[Claims] 1. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [However, X
▲There are mathematical formulas, chemical formulas, tables, etc.▼R_1 is a halogen atom Y is -COOR_2 R_2 represents a lower alkyl group. ] (E)-5-(β-substituted vinyl)-2-
After reacting the ester of thienyl acetic acid with an alkali condensing agent to generate its anion, the general formula (II) R_3Z(II) [where R_3 represents a methyl group or an ethyl group, and Z represents an iodine or bromine. General formula (III), which is characterized by reacting an alkyl halide represented by
Y, R_3 are the same as above] (E)-2-{5-(β-substituted vinyl)-
2-thienyl}fatty acid ester manufacturing method.