Sodium Carbonate → (3R,4S)-tert-butyl 3-(benzyloxycarbonylamino)-4-(bis(4-methoxyphenyl)(phenyl)methoxy)pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of (3R,4S)-tert-butyl 3-azido-4-(bis(4-methoxyphenyl)(phenyl)methoxy)pyrrolidine-1-carboxylate (3.0 g, 5.65 mmol) in anhydrous THF (70 mL) was added triphenylphosphine (2.97 g, 11.3 mmol). The resulting mixture was stirred at ambient temperature for 18 hours. The mixture was concentrated under reduced pressure and to the residue were added methanol (35 mL) and a 0.5 N sodium hydroxide solution (35 mL). The mixture was stirred at ambient temperature 18 hours, and then partitioned between water (35 mL) and ethyl acetate (150 mL). The layers were separated and the aqueous layer was back extracted with ethyl acetate. The combined organic extracts washed with water and brine, dried (MgSO4), filtered and concentrated under reduce pressure. The residue was purified by column chromatography (Biotage 40M; 2.5% MeOH:dichloromethane). To a solution of (3R,4S)-tert-butyl 3-amino-4-(bis(4-methoxyphenyl)(phenyl)methoxy)pyrrolidine-1-carboxylate (2.85 g, 5.65 mmol) in a 50% mixture of 1,4-dioxane/water (20 mL) was added sodium carbonate (0.72 g, 6.78 mmol) and the mixture cooled to 0° C. in an ice bath. Benzyl chloroformate (1 mL, 6.78 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 minutes and then at ambient temperature for 18 hours. The mixture was partitioned between water (20 mL) and diethyl ether (100 mL), and the layers were separated. The organic layer was washed sequentially with water, saturated sodium bicarbonate and brine, then dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 40M 25% ethyl acetate/hexanes) to afford (3R,4S)-tert-butyl 3-(benzyloxycarbonylamino)-4-(bis(4-methoxyphenyl)(phenyl)methoxy)pyrrolidine-1-carboxylate (2.18 g, 60%).

Provenance & Evidence