Triethylamine → HCID 86652377, compound

Participants

Reaction Conditions

Reaction Steps

(S)-2-(1-(4-(benzyloxy)phenyl)pyrrolidin-2-yl)acetonitrile: To a clear, yellow homogeneous solution of 91A (14 g, 49.5 mmol) at 0° C. in methylene chloride (150 mL) was added triethylamine (13.3 mL, 98.9 mmol) and methanesulfonyl chloride (8.5 g, 74 mmol). The reaction mixture stirred at 0° C. becoming cloudy and orange in color. After 1 h, the reaction mixture was diluted with ethyl acetate and water. The combined organics were washed with 1N HCl, saturated sodium bicarbonate and brine, then were dried over MgSO4 and concentrated to yield (S)-(1-(4-(benzyloxy)phenyl)pyrrolidin-2-yl)methyl methanesulfonate (thick brown oil, 15 g, 41.5 mmol). To the solution of (S)-(1-(4-(benzyloxy)phenyl)pyrrolidin-2-yl)methyl methanesulfonate (15 g, 41.5 mmol) in DMSO (50 mL) was added sodium cyanide (6.1 g, 49 mmol) and the mixture was heated to 50° C. After 4 h, the reaction mixture was diluted with 1000 mL of ethyl acetate and 350 mL of water. The layers were extracted and the organic layer was washed twice with 200 mL of water, then 200 mL of brine. The organic layer was dried over MgSO4, filtered and evaporated to dryness to yield 15 g of an orange solid. The residue was purified silica gel column (60-120 mesh) with dichloromethane as eluent to yield 91B (off-white solid, 5 g, 34% yield). LC-MS Anal. Calc'd for C19H20N2O 292. found [M+H] 293.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.45 (5H, m), 6.91 (2H, d, J=8.80 Hz), 6.60 (2H, d, J=8.80 Hz), 5.03 (2H, s), 3.97 (1H, m), 3.42 (1H, m), 3.04 (1H, m), 2.71 (2H, m), 2.14 (2H, m), 1.9 (2H, m).

Provenance & Evidence