(Dimethyl sulfide)trihydroboron → 1-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-aminomethylcyclopentane

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Reaction Steps

To a solution of 0.70 gm of the amide from Step B in 10 mL of THF was added 2.25 mL of 2M borane-dimethylsulfide in THF. The reaction was stirred at room temperature for 16 hours and then warmed at 50° C. for another 6 hours. The excess borane was quenched with dropwise addition of methanol and then 20 mL of methanol and 5 mL of 2N hydrochloric acid were added and the reaction was stirred at room temperature for 24 hours. The mixture was concentrated in vacuo, diluted with water, made basic with 2N sodium hydroxide and extracted twice with methylene chloride. The organic layers were washed with brine, dried over sodium sulfate, combined and evaporated. The residue was purified by FC (methylene chloride, the 5 -10% methanol in methylene chloride) to give 350 mg of title compound. NMR (CDCl3) δ1.33 (d, 3H, J=6.5 Hz), 1.53 (br s, NH2+H2O), 1.5-1.65 (m, 1H), 1.7-1.85 (m, 1H), 1.85-2.0 (m, 2H), 2.0-2.15 (m, 1H), 2.59 (dd, 1H, J=8 and 10 Hz 2.52 and 2.67 (dABq, 2H, J=4.6 and 12.6 Hz), 3.67 (q, 1H, J=6 Hz), 4.45 (q, 1H, J=6.5 Hz), 6.85-6.95 (m, 2H), 6.95-7.05 (m, 2H), 7.38 (s, 2H), 7.64 (s, 1H). Mass spec (ESI): 450(M+1).

Provenance & Evidence