Hydrochloric Acid → (2S,3R)-methyl-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-tert-Butoxycarbonylamino-3-difluoromethoxy-butyric acid methyl ester (3 g, 10.6 mmol) in methanol (40 mL) was added concentrated HCl solution (10 mL) and the reaction was stirred at 50° C. for 1 hour. The reaction was concentrated on a rotary evaporator and the resulting residue was basified with saturated NaHCO3 solution. The aqueous layer was extracted twice with ethyl acetate. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated. To a solution of the crude material in dichloromethane (50 mL) was added diisopropylethylamine (4.2 mL, 24.2 mmol), followed by methyl chloroformate (0.95 mL, 12.3 mmol). The reaction was stirred at room temperature for 2 hours, quenched by the careful addition of saturated NH4Cl solution and diluted with ethyl acetate. The organic layer was separated, washed with water and brine, dried (MgSO4) and concentrated. The crude material was purified by flash chromatography to yield (2S,3R)-methyl-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoate (1.2 g, 47%).

Provenance & Evidence