Sodium Bicarbonate → HCID 86762224, compound

Participants

Reaction Steps

To a solution of racemic tert-butyl 3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-(2-thienyl)pyrrolidine-1-carboxylate (3.8 g, 8.23 mmol) in dichloromethane (206 mL) cooled to 0° C. is added drop wise 1-chloro-N,N,2-trimethylpropenylamine (2.18 mL, 16.46 mmol). The reaction is warmed to room temperature and is stirred for 2 hours. To the reaction mixture is added a saturated solution of sodium bicarbonate and dichloromethane. The mixture is extracted with dichloromethane. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated to give a residue. The residue is purified by silica gel flash chromatography, eluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1) to give the title compound (3.30 g, 90%). ES/MS (m/e): 444 (M+H). The racemic ten-butyl-3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylate (3.2 g, 7.4 mmol) is dissolved in methanol/chloroform (36 ml/25 ml) and is separated into its constituent enantiomers by chiral SFC (Chiralpak OJ-H 50×250 mm; eluent: 25% methanol in 75% CO2; flow 300 g/min at UV 240 nm; column temperature −40° C.; 0.64 g/injection). Analysis of isolated enantiomer (Chiralpak OJ-H 4.6×150 mm; eluent: 25% methanol in 75% CO2; flow 5 mL/min at UV 240 nm, column temperature −35° C.) gave the title compound with Rt=1.5 min, isomer 1, (1.27 g, 39%, >99% ee).

Provenance & Evidence