Synthetic method of florfenicol intermediate cyclic product

Abstract

The embodiment of the invention provides a synthetic method of a florfenicol intermediate cyclic product and belongs to the technical field of chemical synthesis. The method comprises the following steps of: (1) carrying out reduction reaction on D-4-Methylsulfonylphenyl serine ethyl ester and potassium borohydride in an organic solvent at a temperature of -5 to 100 DEG C in the presence of anhydrous calcium chloride serving as a catalyst to obtain a thiamphenicol amine organic solution; adding hydrochloric acid or sulfuric acid to the thiamphenicol amine organic solution and acidifying; controlling the pH to 2-3; steaming out a part of the organic solvent at a reduced pressure; cooling and crystallizing; and separating to obtain thiamphenicol amine hydrochloride or thiamphenicol amine sulfate; (2) dissolving thiamphenicol amine hydrochloride or thiamphenicol amine sulfate into the organic solvent; adjusting the pH to be 7 to 7.5 through alkali; performing cyclization reaction with dichloroacetonitrile under 30 to 70 DEG C; cooling and crystallizing after the reaction is done; and separating to obtain the florfenicol intermediate cyclic product. The synthetic method provided by the invention enables the production cycle to be reduced greatly; and the synthetic yield of the florfenicol intermediate cyclic product reaches more than 90.5%.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, in particular to a synthesis method of a florfenicol intermediate cyclic compound. Background technique [0002] Florfenicol (Florfenicol) Chinese name: fluprofen, florfenicol, florfenicol, Chinese full name: [R--(R1.T)]-2,2-dichloro-N-{fluoro Methyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]ethyl}acetamide is a new broad-spectrum chloramphenicol for veterinary medicine successfully developed in the late 1980s Antibacterial drug, used to treat bacterial diseases of pigs, chickens and fish caused by sensitive bacteria, especially effective for respiratory system infection and intestinal infection. [0003] In the prior art, through its intermediate cyclic compound (the name is D-threo-2-(dichloromethyl)-4,5-dihydro-5-[to-(thysulfonyl)phenyl]- 4-oxazole methanol, whose structural formula is as follows) is fluorinated by Ishikawa fluorinating agent, hydrolyzed under weak acid, and finally ...

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Problems solved by technology

[0008] 1. The production cycle for the synthesis of florfenicol intermediate cyclic compound is long, the total synthesis reaction time is 60-65 hours, and post-processing is difficult

The main reason is that it takes a long time to distill methanol in the later stage (need to complete the basic distillation), it is difficult to distill thoroughly, and the residue after distillation is viscous and difficult to stir, resulting in difficult operation

[0009] 2. The synthetic yield of florfenicol intermediate cyclic compound (based on D-p-thymphenylphenylserine ethyl ester) is low, and the yield is about 85%.

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