1-((Phenylmethoxy)carbonyl)-3-piperidinebutanoic acid → Phenylmethyl 3-(4-hydroxybutyl)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(1-{[(phenylmethyl)oxy]carbonyl}-3-piperidinyl)butanoic acid (commercially available, for example, from Astatech) (5.01 g, 16.41 mmol) in dry THF (40 mL) at 0° C. under nitrogen was added a solution of Borane-THF complex, (1M solution in THF) (49.2 mL, 49.2 mmol), dropwise over 1 hour. The mixture was allowed to stir at 0° C. and gradually allowed to warm to room temperature over 20 hours. The mixture was cooled in an ice bath and cautiously quenched with dropwise addition of MeOH (20 mL), stirred in the cold bath for 2 hours, then quenched further with 10% 2N HCl/MeOH (20 mL), stirred for 1 hour at room temperature and evaporated under reduced pressure. The residue was co-evaporated with methanol several times. The sample was purified by chromatography on silica (100 g, loaded in dichloromethane/EtOAc) using a gradient of 0-100% ethyl acetate-cyclohexane over 30 minutes collecting all 45 mL fractions on the Flashmaster II. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a colourless oil (4.55 g).

Provenance & Evidence