4-Methylmorpholine → 4-{(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-2-oxo-pyrrolidin-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

Stir a solution of 4-[(R)-3-(4′-Carboxy-3,5-dichloro-biphenyl-4-ylmethyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Preparation 25) (0.1 g, 0.18 mmol), 4-(Trifluoromethyl)piperidine Hydrochloride (42 mg, 0.22 mmol), N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (42 mg, 0.22 mmol), 1-Hydroxybenzotriazole (73 mg, 0.22 mmol) and 4-Methylmorpholine (0.08 mL, 0.73 mmol) in CH2Cl2 (3 mL) at room temperature for 6 hr. Quench the reaction with 1N HCl and extract with EtOAc. Wash the organic with brine, dry over MgSO4, and filter. Purify the crude by silica gel column chromatography using Hexanes:EtOAc to elute the pure product. Remove the solvent to afford 0.10 g (80%) of desired product. MS (m/e): 582 (M−BOC+).

Provenance & Evidence