Benzylamine → (3aR,4R,5S,7aS)-2-benzyl-5-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(4-fluorophenyl)octahydro-1H-isoindole

Participants

Reaction Conditions

Reaction Steps

In a pressure tube was placed a solution of crude [(1S,2R,3R,4S)-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexane-1,2-diyl]di(methylene) dimethanesulfonate (step H) in ˜20 mL ethanol and 1.2 mL (˜3 equiv.) benzylamine. The pressure tube was sealed and heated at 150° C. in an oil bath for 3 hr. The tube was cooled to RT and opened. The resulting mixture was transferred to a round bottom flask and the solvent removed under vacuum. The residue was diluted with 100 mL EtOAc, washed with 20 mL 5N aq. NaOH, dried over MgSO4 drying agent, filtered and the solvent was evaporated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with EtOAc to give 1.6 g of the title compound. 1H-NMR (CDCl3): δ: 7.35-7.20 (5 H, m), 7.50 (2 H, s), 6.97 (2 H, m), 6.85 (2 H, t, J=8.2 Hz), 4.42 (1 H, t, J=6.0 Hz), 3.75 (2 H, d, J=13.4 Hz), 3.50 (2 H, d, J=13.4 Hz), 3.30 (1 H, m), 2.96 (1 H, m), 2.52 (3 H, m), 2.19 (2 H, m), 1.98 (1 H, m), 1.97 (1 H, m), 1.86 (2 H, m), 1.57 (1 H, m), 1.33 (3 H, t, J=6.0 Hz), 1.30 (1 H, m). MS: (MH)+ 566.0.

Provenance & Evidence