Hydrochloric Acid → N-[(Phenylmethoxy)-carbonyl]-D-phenylalanyl-L-proline Methyl Ester

Participants

Reaction Steps

To a solution of N-CBZ-D-phenylalanine (47.3 g, 0.158 mmol) in DMF (300 mL) at 0° C., was added L-proline-methylester.HCl (25.0 g, 0.151 mmol), 1-hydroxybenzotriazole hydrate (20.28 g, 0.166 mmol), ethyl-3-(3-dimethylamino)-propyl carbodiimide.HCl (31.8 g, 0.166 mmol) and 4-methylmorpholine (16.0 g, 0.159 mmol). The reaction mixture was stirred for 8 h while allowing the reaction to warm to room temperature. The reaction mixture was poured in water (1.2 L) and extracted with ethyl acetate (3×300 mL). The combined organic extracts were washed as follows: KHSO4 (0.25 M, 2×200 mL), water (1×200 mL), saturated aqueous NaHCO3 (2×200 mL) and saturated NaCl (1×200 mL). The organic layer was dried over MgSO4, filtered and the solvent removed in vacuo to give title compound, 60.9 g (98%), as an oil. MS (M+H)+ =411+.

Provenance & Evidence