RESUMEN

A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.

Asunto(s)

Anticonvulsivantes/síntesis química , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/síntesis química , Proteínas Bacterianas , Hidrogenación , Pregabalina , Estereoisomerismo , Factores de Transcripción