Method of making (S)-(+)-3-(aminomethyl)-5-methylhexanoic acid

摘要

The present invention provides a method of making (S)-(+)-3-(aminomethyl)-5-methylhexanoic acid which comprises condensing isovaleraldehyde with an alkyl cyanoacetate to form a 2-cyano-5-methylhex-2-enoic acid alkyl ester; reacting the 2-cyano-5-methylhex-2-enoic acid alkyl ester with a dialkyl malonate to form 3-isobutylglutaric acid; forming the anhydride of 3-isobutylglutaric acid; reacting the anhydride with ammonia to form (U)-3-(carbamoylmethyl)-5-methylhexanoic acid; reacting (U)-3-(carbamoylmethyl)-5-methylhexanoic acid with (R)-(+)-'alpha'-phenylethylamine to obtain the (R)-(+)-'alpha'- phenylethylamine salt of (R)-(-)-3-(carbamoylmethyl)-5- methylhexanoic acid; combining the salt with an acid to obtain (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid; and reacting the (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid with a Hofmann reagent to obtain (S)-(+)-3-(aminomethyl)-5- methylhexanoic acid.