Method for synthesizing L-norvaline

Abstract

The invention provides a method for synthesizing L-norvaline. The method comprises the following steps: 1, adding acetic acid into a reaction kettle, adding DL-norvaline and D-tartaric acid while stirring, heating to 80DEG C, adding salicylaldehyde, and maintaining the temperature in a range of 80-85DEG C for 10h; 2, cooling to 20-25DEG C after temperature maintenance, keeping the decreased temperature for 1h, and centrifuging to obtain crude L-norvaline and D-tartaric acid; 3, adding petroleum ether to the crude L-norvaline and D-tartaric acid, stirring and washing for 30min, and centrifuging to obtain a purified L-norvaline and D-tartaric acid double salt; 4, heating the double salt in water to 70DEG C in order to completely dissolve the double salt, adjusting the pH value to 7 by using ammonia water, cooling to 20-25DEG C, crystallizing for 2h, centrifuging, and rinsing by using methanol to obtain crude L-norvaline; and 5, heating the crude L-norvaline in water to 80-85DEG C in order to completely dissolve the crude L-norvaline, adding active carbon, decoloring for 1h, filtering, concentrating, cooling to 20-25DEG C, crystallizing for 3h, centrifuging, rinsing with water to obtain wet L-norvaline, and carrying out 60DEG C vacuum drying to obtain dry L-norvaline. The method has the advantages of few steps, good environmental protection property and high yield.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing L-norvaline. Background technique [0002] L-norvaline is white crystalline powder, soluble in hot water and dilute hydrochloric acid, insoluble in ethanol and ether. It is the key intermediate of multiple drugs such as synthetic pradopril, and the existing industrialized method for synthesizing L-norvaline has the following deficiencies: [0003] 1) Use n-butyraldehyde and potassium cyanide as raw materials to synthesize L-norvaline. Because this method requires the use of highly toxic raw material potassium cyanide, firstly, ordinary factories cannot solve the problem, and secondly, management and environmental protection will also have great impact. Difficult, and the final chirality cannot be more than 99.5; [0004] 2) Use DL-norvaline, acetylate it with acetic anhydride and then split it with aminoacylase, because this reso...

AI Technical Summary

Problems solved by technology

[0003] 1) Use n-butyraldehyde and potassium cyanide as raw materials to synthesize L-norvaline. Because this method requires the use of highly toxic raw material potassium cyanide, firstly, ordinary factories cannot solve the problem, and secondly, management and environmental protection will also have great impact. Difficult, and the final chirality cannot be more than 99.5;

[0004] 2) Use DL-norvaline, acetylate it with acetic anhydride and then split it with aminoacylase, because this resolution can only convert 50%, and D-acetylnorvaline needs further racemization Re-split, so the yield is not high;

[0005] 3) Using n-butyraldehyde and acetone cyanohydrin as the main starting materials, n-butyraldehyde and acetone cyanohydrin are cyanated under the action of a basic catalyst; this route is very long, and the final yield is also very high. Low, high cost and not suitable for industrialization