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

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Reaction Steps

Benzyl bromide (17.1 mL, 0.144 mol) and sodium hydride (55% in liquid paraffin, 6.27 g, 0.144 mol) were sequentially added to a solution of (4R)-4-allyl-4-hydroxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one (31.1 g, 0.120 mol) in tetrahydrofuran (300 mL)-dimethylformamide (75 mL) in a nitrogen atmosphere at 0° C. The mixture was stirred at the same temperature for 30 minutes. Methanol (5 mL) was carefully added and stirred until gas was not generated. Then, the reaction was quenched with a saturated ammonium chloride solution (50 mL). The reaction solution was poured into a mixture of ethyl acetate (1000 mL) and water (150 mL), followed by extraction with ethyl acetate (1500 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=3:1→2:1→1:1) to give 41.3 g (99%) of the title compound as a pale yellow oil.

Provenance & Evidence