Diisopropylethylamine → 3,3-bis(4-fluorophenyl)-1-(2-oxo-2-((4aS,7aS)-tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl)ethyl)pyrrolidin-2-one

Participants

Reaction Steps

To a solution of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (Example 58D) (0.331 g, 1 mmol) and (4aS,7aS)-tert-butyl octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate (Example 50B) (0.226 g, 1 mmol) in methylene chloride (20 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.38 g, 1 mmol) and diisopropylethylamine (0.45 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with methylene chloride, and then washed with 1 N HCl, water, 1 N NaOH, and water. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The obtained residue was purified by silica gel chromatography eluting with ethyl acetate to yield the t-butoxycarbonyl-protected title compound. That material was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (2 mL) for 1 hour at room temperature. The reaction mixture was concentrated and partitioned between saturated aqueous NaHCO3 solution and dichloromethane. The organic layer was separated, dried over MgSO4 and concentrated to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.35 (m, 4H), 7.00 (m, 4H), 4.25 (dd, 1H), 3.96 (t, J=16.78 Hz, 1H), 3.47 (m, 7H), 3.00 (m, 1H), 2.78 (m, 2H), 2.63 (m, 1H), 2.27 (m, 1H), 1.72 (m, 2H) 1.45 (m, 2H); MS (ESI+) m/z 440 (M+H)+.

Provenance & Evidence