Preparation method of 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribo-gamma-lactone

A technology of isopropyl dibenzoyl and phosphorylalanine, which is applied in the field of medicine and chemical industry, can solve the problems of production safety hazards and Chen Bengao, and achieve the goals of avoiding explosiveness, increasing safety and reducing production costs Effect
CN103804446AInactive Publication Date: 2014-05-21苏州东南药业股份有限公司
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
苏州东南药业股份有限公司
Publication Date
2014-05-21
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention provides a preparation method of 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribo-gamma-lactone (sofosbuvir). The method comprises the following steps: adding alkali into a mixed solution of L-alanine isopropyl ester or an acid salt thereof and phenyl dichlorophosphate for reacting to obtain (S)-2-phenoxy-chloro-phosphoryl amino isopropyl propionate, reacting the (S)-2-phenoxy-chloro-phosphoryl amino isopropyl propionate with 4-trifluoromethylphenol in the presence of alkali at the temperature of 0-10 DEG C to obtain racemic (S)-2-[(4-trifluoromethyl-phenoxyl)-phenoxy-phosphoryl amino)]alanine isopropyl ester, dissolving the racemic (S)-2-[(4-trifluoromethyl-phenoxyl)-phenoxy-phosphoryl amino)]alanine isopropyl ester into an ether or alkane solvent at the normal temperature, cooling to 50-10 DEG C below zero, and separating (S)-2-[(S)-(4-trifluoromethyl-phenoxy)]-phenoxy-phosphoryl amino)]alanine isopropyl ester out; and reacting the (S)-2-[(S)-(4-trifluoromethyl-phenoxy)]-phenoxy-phosphoryl amino)]alanine isopropyl ester with (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine in the presence of organic alkali with high steric hindrance to obtain the 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribo-gamma-lactone. The method has the advantages of simple steps, mild reaction and suitability for industrial production.
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Description

technical field

[0001] The invention belongs to the field of medicine and chemical industry, and specifically relates to a preparation method of 3,5-dibenzoyl-2-deoxy-2-fluoro-2methyl-D-ribose-γ-lactone (sofosbuvir) . Background technique

[0002] Hepatitis C virus (HCV) infection is a major health problem leading to chronic liver diseases such as cirrhosis and hepatocellular carcinoma, with an estimated 2-15% of individuals worldwide infected with this virus. According to data, there are about 40 million HCV-infected people in China, accounting for 3.2% of my country's population, and there is an increasing trend. According to the World Health Organization, more than 200 million people are infected with HCV worldwide, and the number increases by about 4 million each year. HCV infection is mainly transmitted through blood sources, such as blood and blood product contamination, syringe contamination, unclean sex and mother-to-child transmission. Once infected with HCV, onl...

Claims

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