Iodine → HCID 71548841, compound

Participants

Reaction Steps

To a stirring solution of iodine (354 mg, 1.394 mmol) in dichloromethane (8 mL) was added triphenylphosphine (375 mg, 1.429 mmol). After 5 min triethylamine (0.389 mL, 2.79 mmol) was added. After 5 min a solution of the product from Step A (180 mg, 0.348 mmol) in dichloromethane (3 mL) was added. After stirring at ambient temperature for 1 h, a 1:1 mixture of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulfate (5 mL) was added. The biphasic mixture was stirred for 10 min, the layers were separated and the aqueous phase extracted with dichloromethane (3×5 mL). The combined organic phases were washed with saturated aqueous brine (1×5 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography (silica gel 40 g column) eluting with ethyl acetate/hexane (gradient from 0% to 100%) to give a mixture of diastereomers as a colorless amorphous solid. The isomers were separated via chiral HPLC (ChiralPak AS-H; 40% 2:1 methanol:acetonitrile/carbon dioxide) to afford the first eluting isomer (5R)-5-Benzyl-5-[5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-3-[(1R)-1-phenylethyl]imidazolidine-2,4-dione (2.25 minutes) and the second eluting isomer (5S)-5-Benzyl-5-[5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-3-[(1R)-1-phenylethyl]imidazolidine-2,4-dione (3.45 minutes) as colorless amorphous solids. LC/MS 499.1 (M+1). IC50 value=C rating for the title compound.

Provenance & Evidence