Asymmetric Synthesis of (<i>S</i>)-3-Amino-4-methoxy-butan-1-ol by Way of Reductive Amination

Abstract

A new synthesis of ( S )-3-amino-4-methoxy-butan-1-ol is reported. The synthesis is based on the preparation of the primary, nonprotected enamine of the commercially available β-keto ester methyl 4-methoxy-3-oxo-butanoate and asymmetric catalytic enamine hydrogenation using a Ru-MeOBIPHEP catalyst. Alternatively, the process is performed by asymmetric catalytic reductive amination of the β-keto ester with ammonium acetate and hydrogen using a similar Ru catalyst. Both process versions provided initial ee values of 97−98% which were upgraded to ≥99% by product crystallization. Ester to alcohol conversion was best accomplished by LiBH 4 reduction after transitory Boc protection of the amino group.