Synthesis of (-)-2-amino-6-propionamido tetrahydro benzothiazole

Abstract

The syntyesis of (-)-2-amino-6-propionamido tetrahydro benzothiazole features the adopting common chemical material 4-amin cyclohexanol as initial material, and the six-step process including N-acetylating reaction for protecting amino radical, oxidation with Jones reagent to prepare 4-acetamido cyclohexanone, thiazole annelation, HBr hydrolysis, tartaric acid chiral compound resolution, propionic anhydride acylation. The present invention has mild reaction condition, easy control, simple production process, low production cost, high reaction yield and easy industrial application.

Description

Technical field: [0001] The invention relates to a synthesis method of (-)-2-amino-6-propionamidotetrahydrobenzothiazole, which belongs to the field of fine chemical production. Background technique: [0002] At present, there are two main methods for the synthesis of this product: [0003] One is to use 4-acetylaminocyclohexanone as the starting material, through the bromination reaction of 4-acetylaminocyclohexanone in glacial acetic acid, condensation with thiourea to form a thiazole ring, and free 2-amino-6 -Acetamido-4,5,6,7-tetrahydrobenzothiazole; then hydrolyzed with HBr and converted to 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole hydrochloride; Tartaric acid resolution, propionic anhydride acylation to obtain the product. The weak point of this method is that the mol ratio of the bromination cyclization raw material is 4-acetamidocyclohexanone: bromine: thiourea=1: 1: 2, thiourea is excessive 1 times, causes raw material cost height, reaction temperature The high...

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Problems solved by technology

The weak point of this method is that the mol ratio of the bromination cyclization raw material is 4-acetamidocyclohexanone: bromine: thiourea=1: 1: 2, thiourea is excessive 1 times, causes raw material cost height, reaction temperature The highest is 110°C. After the reaction, the intermediate is freed with alkali, and the yield is low, only 46%, and the product after hydrolysis is its HBr salt, which causes the subsequent product to be converted into hydrochloride. The operation is more complicated, and there are many raw materials. Big waste, low yield

The weak point of this method is that the amino protecting group selected is a benzene ring derivative, the molecule is large, and the cost is high, and the bromination cyclization reaction raw material mol ratio is 4-acetylaminocyclohexanone: bromine: thiourea= 1:1:2, the excess of thiourea is 1 times, the amount of raw materials is large, the reaction temperature is as high as 110°C, the yield of bromination into a ring is only 37%, and the yield of HBr hydrolysis is 82%, so there are many raw materials and a lot of waste , the operation is complex

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