Benzene, 1-bromo-2-(trifluoromethyl)- → HCID 66997586, compound

Participants

Reaction Conditions

Reaction Steps

To a microwave vial under nitrogen was added tert-butyl(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylcarbamate from Example 216 step B (290 mg, 1.281 mmol), 1-bromo-2-(trifluoromethyl)benzene (0.183 mL, 1.345 mmol), potassium phosphate, tribasic (446 mg, 2.56 mmol), tris(dibenzylideneacetone)dipalladium(0) (23.47 mg, 0.026 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-PHOS, 48.9 mg, 0.103 mmol) in t-amyl alcohol (2.0 mL). The reaction was heated at 80° C. for 18 hours. The reaction was diluted with ethyl acetate (35 mL) and quenched with water (75 mL). The organic phase was removed, and the aqueous layer extracted with 50 mL of ethyl acetate. The solvent was removed in vacuo. The crude material was applied to a 24 g silica gel cartridge with ether and purified using 1-50% ethyl acetate/hexanes to give tert-butyl (3aR,4S,6aS)-2-(2-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrol-4-ylcarbamate: 1H NMR (400 MHz, pyridine-d5) δ ppm 7.66 (d, J=7.8, 1H), 7.45 (t, J=7.6, 1H), 7.25 (d, J=8.1, 1H), 7.11 (t, J=7.5, 1H), 4.21 (s, 1H), 3.40 (d, J=9.1, 1H), 3.11 (dd, J=9.1, 6.9, 1H), 3.03-2.88 (m, 2H), 2.69 (d, J=11.5, 2H), 2.17 (dt, J=11.4, 5.7, 1H), 2.04-1.91 (m, 1H), 1.67 (dd, J=18.5, 7.9, 1H), 1.60-1.46 (m, 11H); MS (ESI+) m/z 371 (M+H)+.

Provenance & Evidence