Reaction Steps
To a microwave vial under nitrogen was added tert-butyl methyl((S)-4-methyl-1-((3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylamino)-1-oxopentan-2-yl)carbamate from Step 1 (118 mg, 0.334 mmol), 1-bromo-2-fluorobenzene (0.038 mL, 0.350 mmol), potassium phosphate, tribasic (116 mg, 0.668 mmol), tris(dibenzylideneacetone)dipalladium(0) (6.11 mg, 6.68 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-PHOS, 12.73 mg, 0.027 mmol) in t-amyl alcohol (1.0 mL). The reaction was heated at 80° C. for 18 hours. The solvent was removed and the solids were washed with 2×2 mL of ethyl acetate. The solvent was removed under a stream of nitrogen. The crude material was applied to a 12 g silica gel cartridge with ether and purified using 1-50% ethyl acetate/hexanes to give tert-butyl(S)-1-((3aR,4S,6aS)-2-(2-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-ylamino)-4-methyl-1-oxopentan-2-yl(methyl)carbamate: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.47-8.39 (m, 1H), 7.12 (ddd, J=13.9, 8.0, 1.4, 1H), 7.06 (td, J=7.8, 1.4, 1H), 6.86-6.77 (m, 2H), 5.17 (ddd, J=10.0, 7.5, 1.0, 1H), 4.46-4.35 (m, 1H), 3.65 (d, J=9.4, 1H), 3.30-3.21 (m, 1H), 3.17 (d, J=9.1, 1H), 3.13-3.03 (m, 4H), 2.69-2.57 (m, 2H), 2.11-1.98 (m, 1H), 1.94-1.82 (m, 3H), 1.66-1.55 (m, 2H), 1.48 (s, 9H), 1.39 (dddd, J=21.2, 19.9, 9.7, 4.0, 1H), 0.91 (d, J=6.5, 3H), 0.87 (d, J=6.6, 3H); MS (ESI+) m/z 448 (M+H)+.
