Acetonitrile → HCID 66934476, compound

Participants

Reaction Conditions

Reaction Steps

At −78° C. in a 3 neck flask under argon atmosphere, anhydrous acetonitrile (0.150 g, 3.68 mmol) was added to dry ether (2 mL) followed by dropwise addition of LDA (1.84 mL, 3.68 mmol, 2.0M solution in cyclohexanes). The solution was stirred at −78° C. for 20 min. In a separate flask at 0° C. under argon, BF3Et2O (0.260 g, 0.19 mmol) was added to a solution of (S)-N-((5-chloropyridin-2-yl)(3-fluoro-5-(trifluoromethyl)phenyl)methylene)-2-methylpropane-2-sulfinamide (0.750 g, 1.84 mmol) in dry ether (10 mL). The pre-complexed sulfinylimine solution was transferred to the anion solution via syringe dropwise at −78° C. After 30 min the orange solution was quenched by the addition of 1.0M HCl (ca. 10 mL) and the reaction mixture transferred to a separation funnel and extracted with EtOAc (3×20 mL). The combined organic portions were dried over Na2SO4, decanted, concentrated and the diastereomers purified by silica gel ISCO chromatography on 120 g column, 0-90% EtOAc/hexanes. (S)-N-((R)-1-(5-chloropyridin-2-yl)-2-cyano-1-(3-fluoro-5-(trifluoromethyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide eluted next and was isolated as the major product (0.23 mg, 28% yield). Rf0.8 (Hexane:EtOAc 1:1) LCMS: 1.84 min [M+1] 448.1 (2 min gradient, MeOH/H2O 0.1% TFA); HPLC: 3.58 min (4 min gradient, MeOH/H2O 0.2% PPA); Purity 99%; NMR: 400 MHz 1H (CDCl3) 8.62 ppm, d, J=2.6 Hz; 7.73 ppm, dd, J=2.6 and J=8.8 Hz; 7.38, 1H, s; 7.32 ppm, 1H, d, J=7.9 Hz; 7.20 ppm, 2H, d, J=8.8 Hz; 5.87 ppm, 1H, s; 3.76 ppm, 1H, d, J=16.7 Hz; 3.67 ppm, 1H, d, J=16.7 Hz; 1.36 ppm, 3H, s. (S)-N-((S)-1-(5-chloropyridin-2-yl)-2-cyano-1-(3-fluoro-5-(trifluoromethyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide eluted last and was isolated as the a pale yellow oil (0.088 mg, 11% yield). Rf0.7 (Hexane:EtOAc 1:1) LCMS: 1.90 min [M+1] 448.1 (2 min gradient, MeOH/H2O 0.1% TFA); HPLC: 3.65 min (4 min gradient, MeOH/H2O 0.2% PPA); Purity 99%.

Provenance & Evidence