4-Methylmorpholine → (R)-3-[3,5-dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(tetrahydro-pyran-4-yl)-pyrrolidin-2-one

Participants

Reaction Steps

Treat a solution of 3′,5′-dichloro-4′-[(R)-2-oxo-1-(tetrahydro-pyran-4-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (0.25 g, 0.56 mmol), 4-(trifluoromethyl)piperidine hydrochloride (0.13 g, 0.67 mmol), 1-hydroxybenzotriazole (0.23 g, 0.67 mmol), and 4-methylmorpholine (0.18 mL, 1.67 mmol) in dichloromethane (10 mL) with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.13 g, 0.67 mmol) and stir at room temperature for 6 hr. Quench the reaction with 1N hydrochloric acid and extract with ethyl acetate. Wash the organic layer with brine, dry over magnesium sulfate, and filter. Purify the crude material by silica gel column chromatography using hexanes:ethyl acetate to afford 0.23 g (72%) of desired product: MS (m/z): 583 (M+).

Provenance & Evidence