A method for synthesizing a brivaracetam chiral intermediate (R)-3-cyanohexanoic acid by catalyzing the hydrolysis of 3-cyanohexanitile using an enzyme with nitile hydrolysis activity, and the enzyme with nitrile hydrolysis activity is obtained by carrying out a single mutation or a double mutation on an amino acid at position 140 or an amino acid at position 175 in an amino acid sequence as set forth in SEQ ID NO.2. Compared with a wild type, the nitrilase mutant has the activity increased by 10 times, an ee value increased to 300 or more from 39, a substrate conversion rate of 45%, and a product ee which can reach 98.5%, and the yield of (R)-3-aminomethyl-hexanoic acid by catalytic hydrogenation synthesis using (R)-3-cyanohexanoic acid reaches 85% or more. This features a short synthesis route, mild reaction conditions, and high atom economy, and can be applied to the industrial synthesis of the brivaracetam intermediate.

A method for synthesizing a brivaracetam chiral intermediate (R)-3-cyanohexanoic acid by catalyzing the hydrolysis of 3-cyanohexanitile using an enzyme with nitile hydrolysis activity, and the enzyme with nitrile hydrolysis activity is obtained by carrying out a single mutation or a double mutation on an amino acid at position 140 or an amino acid at position 175 in an amino acid sequence as set forth in SEQ ID NO.2. Compared with a wild type, the nitrilase mutant has the activity increased by 10 times, an ee value increased to 300 or more from 39, a substrate conversion rate of 45%, and a product ee which can reach 98.5%, and the yield of (R)-3-aminomethyl-hexanoic acid by catalytic hydrogenation synthesis using (R)-3-cyanohexanoic acid reaches 85% or more. This features a short synthesis route, mild reaction conditions, and high atom economy, and can be applied to the industrial synthesis of the brivaracetam intermediate.

A process for preparing valpromide of formula I and sodium valproate of formula II which comprises: cyanoacetate and 1-chloropropane are subjected to composite catalytic dipropylation in the presence of alkali to obtain 2-cyano-2-valproate of formula III; 2-cyano-2-valproate is hydrolyzed and deacidified to give propylvaleronitrile of formula V; propylvaleronitrile is alcoholized in the presence of acid to give valpromide of formula I and valproate ester of formula VI; and valproate ester is hydrolyzed in a sodium hydroxide solution to afford sodium valproate of formula II.

A process for preparing valpromide of formula I and sodium valproate of formula II which comprises: cyanoacetate and 1-chloropropane are subjected to composite catalytic dipropylation in the presence of alkali to obtain 2-cyano-2-valproate of formula III; 2-cyano-2-valproate is hydrolyzed and deacidified to give propylvaleronitrile of formula V; propylvaleronitrile is alcoholized in the presence of acid to give valpromide of formula I and valproate ester of formula VI; and valproate ester is hydrolyzed in a sodium hydroxide solution to afford sodium valproate of formula II.