HCID 68312472, compound → HCID 68312643, compound

Participants

Reaction Steps

Example 17A (800 mg, 2.97 mmol) and Example 105C (498 mg, 2.97 mmol) were dissolved in methanol (20 mL) and triethylamine (0.453 mL, 3.27 mmol). The yellow solution was stirred at ambient temperature for 90 minutes, followed by the addition of sodium borohydride (247 mg, 6.54 mmol). The reaction mixture was stirred over the weekend at ambient temperature, quenched with 100 mL 1.0 N NaOH, and extracted twice with 100 mL dichloromethane, dried over Na2SO4, filtered, and concentrated to obtain (R)-3-[({3-fluoro-6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}methylene)amino]-2,4-dimethylpentan-2-ol (1.147 g, 3.00 mmol) as an orange oil. The imine (1.147 g, 3.00 mmol) in methanol (20 mL) was added to Raney Nickel (1.147 g) in a 50 mL pressure bottle. The mixture was pressurized with hydrogen (30 psi), and stirred for 48 hours at ambient temperature. The mixture was filtered through a nylon membrane, concentrated, and chromatographed on a Grace Reveleris 40 g column, eluted with 0-20% EtOAc in dichloromethane (30 mL/min) to provide the title compound (0.629 g, 1.636 mmol, 54.6% yield) as a colorless oil. MS (ESI+) m/z 385.0 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 8.29 (d, J=8.2, 2H), 8.06 (dd, J=8.7, 3.7, 1H), 7.92-7.78 (m, 3H), 4.25 (s, 1H), 4.16-3.99 (m, 2H), 2.36 (q, J=6.2, 1H), 2.26 (dd, J=5.9, 2.4, 1H), 2.03-1.89 (m, 1H), 1.11 (d, J=9.2, 6H), 0.93 (dd, J=6.8, 5.8, 6H).

Provenance & Evidence