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

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.

1. stirringstirred until gas
2. customThen, the reaction was quenched with a saturated ammonium chloride solution (10 mL)
3. additionThe reaction solution was poured into a mixture of ethyl acetate (100 mL) and water (100 mL)
4. extractionfollowed by extraction with ethyl acetate (800 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=4:1→2:1→1:1)

ORD record

ord-a99e29624cfa4724839d723a30899bbb

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2