Preparation method of 5-bromo-2-chloro-benzoic acid as a synthetic raw material for hypoglycemic drugs
AssigneeZhejiang Ausun Pharmaceutical Co., Ltd.
InventorsYunfeng LI, Zhiguo ZHENG
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Abstract
The invention relates to a preparation method and application of 5-bromo-2-chloro-benzoic acid as a synthetic raw material of a hypoglycemic agent. Specifically, the 5-bromo-2-chloro-benzoic acid is prepared by taking a 5-bromo-2-aminobenzoic acid derivative as an initial raw material through two steps of reactions of diazotization, chlorination and hydrolysis, and the obtained product has the advantages of few isomer impurities, high reaction yield, good purity, low cost and suitability for industrial production. The invention also relates to the application of the 5-bromo-2-amino-benzoic acid in preparing antidiabetic drugs.
Claims19
A process for preparing the compound 5-bromo-2-chlorobenzoic acid of formula I,
- step (1):
- diazotizing and chlorinating the compound of formula III to prepare the compound of formula II, and
- step (2):
- hydrolyzing the compound of formula II to obtain the compound of formula I, wherein:
- R is selected from:
- C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, C6-10aryl, C6-10aryl-C1-6alkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, 5-10 membered heteroaryl-C1-6alkyl, 3-12 membered heterocycloalkyl-C1-6alkyl, C1-6alkoxycarbonyl, C1-6alkoxycarbonyl-C1-6alkyl, C6-10aryl-C1-6alkoxycarbonyl, C6-10aryl-C1-6alkoxycarbonyl-C1-6alkyl, each of which is optionally substituted with one or more groups independently selected from halogen, amino, —NH(C1-6alkyl), —N(C1-6alkyl)2, hydroxy, C1-6alkyl, C1-6alkoxy, halo-C1-6alkyl, halo-C1-6alkoxy, C3-8cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, or 3-12 membered heterocycloalkyl;
- alternatively, when R is H, step (1) as described above is carried out to directly obtain the compound of formula I.
A process for preparing the compound of formula VI, comprising the steps of:
- step (3):
- reacting the compound of formula I with the compound of formula VII through Friedel-crafts acylation reaction to prepare the compound of formula V,
- wherein R1 is selected from:
- H, C1-6alkyl, such as methyl or ethyl, 3-tetrahydrofuranyl, 3-S-tetrahydrofuranyl or 3-R-tetrahydrofuranyl;
- and
- step (4):
- reducing the compound of formula V to obtain the compound of formula VI.
Dependencies are inferred from the claim text.