Dimethylformamide → (4R)-4-Allyl-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

Participants

Reaction Steps

Methyl iodide (1.87 mL, 30.1 mmol) and sodium hydride (55% in liquid paraffin, 1.31 g, 30.1 mol) were sequentially added to a solution of (4R)-4-allyl-4-hydroxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one (7.09 g, 27.3 mmol) in tetrahydrofuran (80 mL)-dimethylformamide (20 mL) in a nitrogen atmosphere at 0° C. The mixture was heated to room temperature and stirred for one hour. Methanol (2 mL) was carefully added and stirred until gas was not generated. Then, the reaction was quenched with a saturated ammonium chloride solution (10 mL). The reaction solution was poured into a mixture of ethyl acetate (100 mL) and water (100 mL), followed by extraction with ethyl acetate (800 mL). The organic layer was sequentially washed with water (200 mL) and brine (200 mL×2), dried over anhydrous sodium sulfate, and filtered. The filtrate was then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→2:1→1:1) to give 7.42 g (99%) of the title compound as a colorless oil.

Provenance & Evidence