Stereoselective reduction of 2- or 3-substituted 4-piperidones with sodium borohydride

摘要

A stereoselective reduction of 2- or 3-substituted 4-piperidones of the formulawhere R₁ is hydrogen, loweralkyl or benzyl and R₂ is methyl or ethyl, to the di-equatorial isomer of the corresponding 4-piperidinol is described. Said reduction is conducted by use of sodium borohydride in a protic solvent medium at a temperature substantially lower than ambient temperature in the presence of an effective amount of an inorganic acid. Under favorable reaction conditions, the stereoselectivity of the reduction is so high that simple crystallization of the reaction product affords the pure isomer in a commercially acceptable and advantageous process.