Preparation method of 2,4,5-trifluorophenylacetic acid

A technology of trifluorophenylacetic acid and fluoroborate, which is applied in 2 fields, can solve problems such as poor safety, and achieve the effect of high safety, good comprehensive effect and less by-products
CN108383718AInactive Publication Date: 2018-08-10江苏八巨药业有限公司
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
江苏八巨药业有限公司
Publication Date
2018-08-10
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a preparation method of 2,4,5-trifluorophenylacetic acid, belongs to the technical field of drug intermediate synthesizing, and aims to solve the problem that existing raw materials are high in risks. The method includes: allowing 2-methyl-4-nitrobenzoic acid to have reaction with nitrite under the effect of strong acid to generate diazotizing salt, adding hydrofluoric acid or fluoborate to perform fluorination, and performing pyrolysis to obtain a compound as shown in formula II; in the presence of an acid-binding agent, allowing the compound as shown in formula II tohave acylation reaction with halogenated acetyl chloride to obtain a compound as shown in formula III; under the effect of alkali metal alkoxide, allowing the compound as shown in formula III to havereaction with alcohol to obtain a compound as shown in formula IV; performing hydrolysis and decarboxylation on the compound as shown in formula IV in an acid system, performing reduction, and then performing diazotization and pyrolysis to obtain the 2,4,5-trifluorophenylacetic acid. The preparation method has the advantages that raw material conversion rate is increased, quality requirements onproduct yield and purity are satisfied, and high final-product total yield is achieved.
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Description

technical field

[0001] The invention relates to a preparation method of 2,4,5-trifluorophenylacetic acid, belonging to the technical field of pharmaceutical intermediate synthesis. Background technique

[0002] Sitagliptin is a dipeptidyl peptidase Ⅳ (DDP-4) inhibitor drug used to treat type Ⅱ diabetes. It is a new type of hypoglycemic drug. Equivalent to market demand. And 2,4,5-trifluoroacetic acid, as a key intermediate in the synthesis of sitagliptin, has broad market prospects.

[0003] In the existing literature, there are mainly the following routes for the synthesis of 2,4,5-trifluoroacetic acid. Such as the Chinese patent (authorized announcement number: CN104387259B) discloses a kind of trifluorobromobenzene first converted into a Grignard reagent, then in the presence of TMEDA with diethyl oxalate through addition reaction, and then with hydrazine hydrate / potassium hydroxide / Diethylene glycol reaction, after acidification to the corresponding 2,4,5-trifluoroac...

Claims

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