Lithiumtriethylborohydride → HCID 23582540, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-methyl 4-(2-(4-fluoro-3-(trifluoromethyl)benzamido)-2-(4-fluoro-3-isopropoxyphenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)benzoate (20 mg, 0.027 mmol) in THF (2 mL) at −78° C. was added a solution of lithium triethylborohydride (1.0 M in THF, 0.5 mL, 0.5 mmol). The reaction mixture was stirred at −78° C. for 1.5 h. The reaction was quenched by the addition of 1 N NaOH (1 mL) and diluted with EtOAc (15 mL). The organic portion was washed with sat. NaCl (2×10 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (YMC Sunfire 5μ C18 30×100 mm column, eluting with 20-90% MeOH/H2O containing 0.1% TFA, 10 min gradient, flow rate 40 mL/min, wavelength 220 nm) to yield (R)-4-fluoro-N-(1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-(4-(hydroxymethyl)phenyl)ethyl)-3-(trifluoromethyl)benzamide (Example 348, 13 mg, 78% yield) as a colorless film. LCMS: RT=2.17 min [M+H] 704.1 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.1% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.0 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.91 (1H, d, J=6.59 Hz), 7.85-7.87 (1H, m) 7.26-7.31 (1H, m), 7.16 (2H, d, J=7.91 Hz), 6.93-7.05 (4H, m), 6.68-6.73 (3H, m), 6.60-6.66 (2H, m), 5.75-6.01 (1H, m), 4.64 (3H, s), 4.35 (1H, m), 4.06 (1H, d, J=13.2 Hz), 3.74 (1H, d, J=13.2 Hz), 1.29 (3H, d, J=6.15 Hz), 1.26 (1H, s), 1.23 (3H, d, J=6.15 Hz).

Provenance & Evidence