Sodium borohydride → N-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-hydroxybutanamide

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Reaction Steps

To a solution of (R)—N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-oxobutanamide (Example 251, 51 mg, 0.1 mmol), in MeOH (1 mL) was added NaBH4 (10 mL, 0.26 mmol). The reaction mixture was stirred at rt for 1 h and concentrated under reduced pressure. The residue was purified by preparative HPLC (Axia luna column, 30×100 mm, 40-100% MeOH/H2O with 0.1% TFA over 10 min, flow rate 40 mL/min, monitoring at 220 nm) to yield N—((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-hydroxybutanamide (Example 330) as a pale yellow oil (28 mg, 55% yield). LCMS: RT=2.66 min [M+H] 512.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.13-7.23 (3H, m), 7.02-7.08 (2H, m, J=4.96, 4.56, 4.56, 2.43, 2.43 Hz), 6.96-7.02 (2H, m), 6.85-6.93 (4H, m), 6.67 (2H, d, J=7.07 Hz), 5.87 (1H, t, J=2.78 Hz), 4.10-4.20 (1H, m), 3.95 (1H, dd, J=12.76, 10.74 Hz), 3.73 (1H, dd, J=12.76, 10.74 Hz), 2.32-2.38 (2H, m), 1.22 (3H, d, J=6.32 Hz).

Provenance & Evidence