反应详情

While under an argon atmosphere, a solution of benzyl 4-(methoxy(methyl) carbamoyl)piperidine-1-carboxylate (15.0 g, 49.0 mmol) in THF (100 mL) was cooled to −78° C. (dry ice/acetone bath) and treated with 3-butenylmagnesium bromide (250 mL, 0.5 M sol. in THF, 125 mmol, Aldrich) via canula. After the addition was complete, the cooling bath was removed allowing the solution to slowly warm to room temperature. After stirring overnight (16 h), the reaction mixture was quenched with 0.1N HCl (200 mL) and diluted with ethyl acetate (300 mL). After stirring an additional 5 min, the organic phase was separated, washed with saturated sodium bicarbonate (200 mL), dried over MgSO4, filtered and concentrated. Purification by MPLC (100 g column, 20-50% ethyl acetate in heptane) gave benzyl 4-pent-4-enoylpiperidine-1-carboxylate (14.5, 98%) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 7.38-7.32 (m, 5H), 5.79 (dddd, J1=17.1 Hz, J2=10.2 Hz, J3=6.9 Hz, J4=6.6 Hz, 1H), 5.12 (s, 2H), 5.02 (dd, J1=17.1 Hz, J2=1.5 Hz, 1H), 4.97 (dd, J1=10.2 Hz, J2=1.5 Hz, 1H), 4.28-4.10 (m, 2H), 2.86 (br t, J=12 Hz, 2H), 2.58-2.43 (m, 3H), 2.35-2.28 (m, 2H), 1.9-1.74 (m, 2H), 1.62-1.48 (m, 2H). ESI MS found for C18H23NO3 m/z [302.3 (M+1), 324.1 (M+23)].

1. additionAfter the addition
2. customthe cooling bath was removed
3. customthe reaction mixture was quenched with 0.1N HCl (200 mL)
4. additiondiluted with ethyl acetate (300 mL)
5. stirringAfter stirring an additional 5 min
6. customthe organic phase was separated
7. washwashed with saturated sodium bicarbonate (200 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by MPLC (100 g column, 20-50% ethyl acetate in heptane)