Ammonium Chloride → tert-Butyl 4-carbamoyl-4-methylpiperidine-1-carboxylate

Participants

Reaction Steps

A solution of 1-(tert-butoxycarbonyl)-4-methylpiperidine-4-carboxylic acid (1.00 g, 4.00 mmol) in DMF (41 mL) and DIPEA (2.9 mL, 17 mmol) was treated with HATU (2.4 g, 6.3 mmol). The solution was stirred for 20 minutes and NH4Cl (0.450 g, 8.40 mmol) was added. The mixture was stirred overnight and then evaporated to dryness. The residue was partitioned between EtOAc (100 mL) and water (150 mL). The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with HCl (1.0 N solution in water), saturated aqueous NaHCO3 solution, water and brine; dried over Na2SO4; filtered and concentrated. The residue was purified by column chromatography (SiO2, 10% MeOH in DCM) to give tert-butyl 4-carbamoyl-4-methylpiperidine-1-carboxylate (781 mg, 78%). LC-MS: (FA) ES+ 265 (M+Na).

Provenance & Evidence