Sodium hydride → 4-Tert-butoxycarbonylamino-4-(4-chloro-benzyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (60% suspension in oil, 4.9 mg, 0.11 mmol) was added in small portions to a cooled (0° C.) solution of 4-tert-butoxycarbonylamino-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (19 mg, 0.057 mmol) in dry DMF (0.2 mL). The suspension was stirred vigorously at 0° C. for 15 min followed by addition of 4-chlorobenzyl bromide (14 mg, 0.066 mmol). After stirring for 45 min at 0° C., the reaction mixture was warmed to rt. When TLC showed complete consumption of the starting material, the reaction mixture was partioned between ethyl acetate (5 mL) and water (2 mL). The aqueous phase was further extracted with ethyl acetate (5 mL). The combined organic layers were dried (Mg2SO4), filtered and concentrated. Flash column chromatography on silica, eluting with 1% methanol in dichloromethane, gave 4-tert-butoxycarbonylamino-4-(4-chloro-benzyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (6 mg, 0.013 mmol, 22%). LC-MS (LCT2) m/z 477 [M+Na+], Rt 8.74 min.

Provenance & Evidence