4-Methylmorpholine → HCID 86587232, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-[(R)-1-{3-(1-tertbutoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-amino-β-alanine (207 mg, 0.45 mmol) in acetonitrile (7 mL) was added monosilylacetamide (0.8 g), then the mixture was stirred for 30 minutes at 45° C. After the mixture was allowed to cool to room temperature, N-methylmorpholine (50 mL, 0.45 mmol) and a solution of cyclopropylmethyl chloroformate (1 mmol) in dichloromethane (2 mL), which was prepared from cyclopropanemethanol, triphosgene and pyridine, was added successively via syringe. After stirring for 2 hours, the mixture was acidified with 20% aqueous KHSO4 solution, extracted with ethyl acetate and dried over sodium sulfate. After evaporation of the solvent, the residue was treated with 4N hydrochloric acid in ethyl acetate. The insoluble material was collected by filtration, dried and dissolved in water. The solution was neutralized with a saturated aqueous NaHCO3 solution, purified by an ODS column chromatography using Daisogel-120SP (10% CH3CN/water) and freeze-dried to give N-[(R)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-(cyclopropylmethyloxycarbonyl)amino-β-alanine (120 mg, 47.4%) as a white powder.

Provenance & Evidence