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

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.

1. stirringstirred until gas
2. customThen, the reaction was quenched with a saturated ammonium chloride solution (50 mL)
3. additionThe reaction solution was poured into a mixture of ethyl acetate (1000 mL) and water (150 mL)
4. extractionfollowed by extraction with ethyl acetate (1500 mL)
5. washThe organic layer was sequentially washed with water (200 mL) and brine (200 mL×2)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was then concentrated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→2:1→1:1)

ORD record

ord-df56a013c8ee4ef7a52f2a534bb3d134

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2