Benzaldehyde → (S)-1-[2-Benzylamino-3-(3,4-dichlorobenzyloxy)propionyl]-4-(2-keto-1-benzimidazolinyl)piperidine Hydrochloride

Participants

Reaction Steps

Methanolic hydrogen chloride (4M, 2 mL) was added to a solution of (S)-1-[2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]-4-(2-keto-1-benzimidazolinyl)piperidine (298 mg, 0.53 mmol) in methanol (2 mL) and the mixture was stirred at room temperature for 5 h. The solvent was evaporated under reduced pressure, dichloromethane (5 mL), triethylamine (0.148 mL, 107 mg, 1.06 mmol), benzaldehyde (0.065 mL, 67 mg, 0.64 mmol) and magnesium sulfate (300 mg) were added. The mixture was stirred at room temperature for 4 h., filtered and the solvent was evaporated under reduced pressure. Methanol (5 mL) was added, the mixture was cooled to 0° C. and sodium borohydride (40 mg, 1.06 mmol) was added. The mixture was stirred at room temperature for 1 h., aqueous sodium hydrogen carbonate (saturated, 20 mL) and water (10 mL) were added and the mixture was extracted with dichloromethane (3×20 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (Aq.) (99:1:0.1 increasing to 95:5:0.5). The residue was dissolved in methanol (5 mL), cooled to 0° C. and methanolic hydrogen chloride (1M, 0.44 mL) was added. The solvent was evaporated under reduced pressure and the residue was triturated with ether (5 mL). The solid was collected and dried in vacuo to give the title compound as a colorless solid (212 mg, 68%), m.p. 148°-151° C. Found: C, 57.18; H, 5.29; N, 9.27. C29H30Cl2N4O3.HCl.H2O requires: C, 57.29; H, 5.47; N, 9.22%. m/e (ES+) 553 (MH+).

Provenance & Evidence