Reaction Steps
To a round bottom flask under argon was added 4-((1S,4R)-6-oxo-2-azabicyclo[2.2.1]heptan-2-yl)benzonitrile (272 mg, 1.282 mmol), tert-butyl (1R,2R)-2-aminocyclohexylcarbamate (330 mg, 1.538 mmol), CH2Cl2 (6.4 ml), solid anhydrous Na2SO4 (1 gm) and HOAc (1 drop). Argon was bubbled through the reaction mixture for 1 min and then the reaction was stirred under argon at rt for 1 hr. After this time, sodium triacetoxy borohydride (815 mg, 3.84 mmol) was added to the reaction which was then stirred at rt overnight. The reaction mixture was then diluted with CH2Cl2. The resulting solution was wash with saturated aqueous NaHCO3, water and saturated aqueous NaCl. The organic layer was separated, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex. The fractions containing the desired product were concentrated to give tert-butyl (1R,2R)-2-((1R,4R,6S)-2-(4-cyanophenyl)-2-azabicyclo[2.2.1]heptan-6-ylamino)cyclohexylcarbamate (466 mg, 1.135 mmol, 89% yield). Anal. Calcd. for C24H34N4O2 m/z 410.5, found: 411.3 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.45 (2 H, d, J=8.8 Hz), 6.55 (2 H, d, J=8.8 Hz), 4.26 (1 H, s), 3.65 (1 H, br. s.), 3.47-3.41 (1 H, m), 3.30 (1 H, dt, J=8.8, 3.0 Hz), 3.15 (1 H, d, J=8.8 Hz), 2.98 (1 H, d, J=8.2 Hz), 2.64 (1 H, s), 2.29-2.19 (2 H, m), 2.10-2.02 (1 H, m), 2.01-1.93 (1 H, m), 1.74-1.59 (4 H, m), 1.45-1.37 (1 H, m), 1.35 (9 H, s), 1.30-1.18 (2 H, m), 1.09- -0.93 (2 H, m), 0.90 (1 H, ddd, J=12.9, 3.8, 3.6 Hz).
