(R)-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-oxobutanamide → HCID 178468380, compound

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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, 62 mg, 0.12 mmol), in acetic acid (0.5 mL) was added dropwise a solution of NaNO2 (25 mg, 0.36 mmol) in H2O (0.5 mL). The reaction mixture was stirred at rt for 10 min and diluted with H2O (10 mL). The aqueous portion was extracted with EtOAc (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to yield (R)—N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-2-(hydroxyimino)-3-oxobutanamide (Example 331) as a yellow solid (65 mg, 100% yield). LCMS: RT=1.99 min [M+H] 539.4 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 10.07 (1H, s), 7.15-7.21 (2H, m), 7.07-7.14 (7H, m), 7.00-7.05 (4H, m), 6.84-6.96 (6H, m), 6.55-6.60 (2H, m), 5.88 (1H, t, J=2.78 Hz), 3.91 (1H, d, J=13.14 Hz), 3.72-3.80 (1H, m), 2.52 (3H, s).

Provenance & Evidence