反应详情

In a 500 mL single necked round bottomed flask, a solution of tert-butyl (3R)-3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate (7.00 g, 27.1 mmol) in tetrahydrofuran (100 mL) was cooled to 0° C. and treated with 0.5 M THF solution of 3-butenylmagnesium bromide (130 mL, 65 mmol) via a pressure equalizing addition funnel over a period of 20 minutes. Once the addition was complete, the cooling bath was removed and the mixture was allowed to warm to room temperature and stir for an additional 4 h. The reaction mixture was carefully quenched with 1 N HCl (300 mL) and stirred for an additional 20 min. The aqueous layer was extracted with ethyl acetate (3×200 mL) and the combined organic layers were dried over Na2SO4, filtered and concentrated to a yellow oil. Purification of the crude product by flash column chromatography (silica gel, 10% ethyl acetate in hexanes) afforded tert-butyl (3R)-3-hex-5-enoylpyrrolidine-1-carboxylate (6.62 g; 96%) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 5.73-5.69 (m, 1H), 4.99-4.91 (m, 2H), 3.61-3.42 (m, 2H), 3.13-3.05 (m, 1H), 2.50 (t, J=7.2 Hz, 2H), 2.26 (q, J=7.2 Hz, 2H), 2.11-1.90 (m, 3H), 1.38 (s, 9H); ESI MS found for C14H23NO3 m/z [154.1 (M+1-Boc)].

1. additionaddition funnel over a period of 20 minutes
2. additionOnce the addition
3. customthe cooling bath was removed
4. customThe reaction mixture was carefully quenched with 1 N HCl (300 mL)
5. stirringstirred for an additional 20 min
6. extractionThe aqueous layer was extracted with ethyl acetate (3×200 mL)
7. dry with materialthe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated to a yellow oil
10. customPurification of the crude product by flash column chromatography (silica gel, 10% ethyl acetate in hexanes)