4-Methylmorpholine → HCID 2759570, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-[3(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-amino-β-alanine (250 mg, 0.55 mmol) in acetonitrile (8 mL) was added monosilylacetamide (1.0 g), then the mixture was stirred for 20 minutes at 45° C. After the mixture was allowed to cool to 0° C., N-methylmorpholine (73 mL, 0.66 mmol) and a solution of 4-methoxycyclohexanecarbonyl chloride (0.66 mmol) in dichloromethane (2 mL), which was prepared from 4-methoxycyclohexanecarboxylic acid, oxalyl chloride and N,N-dimethylformamide, were added successively via syringe. After stirring at ambient temperature for 4 hours, the mixture was 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-[3(R)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-(4-methoxycyclohexanecarbonyl)amino-β-alanine (244.4 mg, 89.8%) as a white powder.

Provenance & Evidence