反应详情

(R)—N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide was prepared by the methods described in Procedures 5 yielding a 3:1 diastereomeric mixture of (R)—N—((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide and (S)—N—((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide in 90% yield. The diastereomers were separated by Chiralcel AD column chromatography elution with Heptane IPA (68% yield). Analytical data and yield for diastereomers in here. Isomer A: LCMS: [M+H] 560.2, retention time=4.08 min (Phenomenex Luna C18 5μ column, eluting with 10-90% aqueous methanol containing 0.1% TFA over a 4 minute gradient, flow rate 5 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.23 (s, 9H), 3.63 (d, J=12 Hz, 1H), 3.73 (s, 3H), 3.89 (d, J=12 Hz, 1H), 5.94 (tt, J=53, 2.4 Hz, 1H), 6.67-6.74 (m, 2H), 6.96-7.03 (m, 3H), 7.36-7.14 (m, 6H) ppm. Chiral HPLC: RT=8.21 min (Chiral AD column 4.6×250 mm; 20% Isocratic; Solvent A=Heptane, Solvent B=0.1% DEA in IPA). Isomer B: LCMS: RT=4.022 min [M+H] 560.2 (4 min 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 1.20 (s, 9H) 3.56 (d, J=12.09 Hz, 1H) 3.77 (s, 3H) 3.98 (d, J=12.64 Hz, 1H) 4.20 (s, 1H) 5.69-6.00 (m, 1H) 6.67-6.74 (m, 2H) 6.80-6.89 (m, 2H) 6.91 (d, J=7.70 Hz, 2H) 7.02-7.08 (m, 1H) 7.10 (s, 1H) 7.11-7.20 (m, 3H). Chiral HPLC: RT=10.34 min (Chiral AD column 4.6×250 mm; 20% Isocratic; Solvent A=Heptane, Solvent B=0.1% DEA in IPA).