Hydrochloric Acid → Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Participants

Reaction Steps

To 5 g of N-BOC-isonipecotic acid (21.8 mmol, Bachem) dissolved in 100 ml THF, cooled in a dry ice/acetone bath, was slowly added 43.6 ml 1 M borane-THF complex in THF (43.6 mmol). The reaction was stirred to −40 C and then replaced with an ice/water bath. After 3 hours the reaction was neutralized by careful addition of water and then worked up by addition of ethyl acetate and 1 M HCl. The layers were separated and the aqueous layer was extracted one more time with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over sodium sulfate and evaporated to give 4.9 g 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (MS: M+H=238).

Provenance & Evidence