반응 #57362

반응 방정식

6-Methoxy-2,3,4,5-tetrahydropyridine

lithium diisopropylamine

methyl 3-(4-fluorophenyl)-2-isobutyrylacrylate

→

methyl 2-[(4-fluorophenyl)-(2-methoxy-3,4,5,6-tetrahydro-pyridin-3-yl)-methyl]-4-methyl-3-oxo-pentanoate

수율 106.5%

용매

THF

반응 조건

후처리

1. 1
   workup.STIRRINGAfter stirring at −60° C. for 1 h
2. 2
   기타the temperature below −50° C
3. 3
   기타The reaction was quenched with saturated ammonium chloride (750 mL) after the reaction
4. 4
   workup.STIRRINGhad stirred at −60° C. for 35 min
5. 5
   온도After the reaction mixture had warmed to room temperature
6. 6
   workup.ADDITIONethyl acetate was added
7. 7
   기타the mixture transferred to a separatory funnel
8. 8
   추출The mixture was extracted with ethyl acetate (2×1 L)
9. 9
   세척The combined organic layers were washed with 50% saturated ammonium chloride solution, water, and brine
10. 10
    건조dried over magnesium sulfate
11. 11
    농축and concentrated in vacuo

실험 절차

6-Methoxy-2,3,4,5-tetrahydropyridine (102.7 g, 0.91 mole) was added over 25 min to a solution of lithium diisopropylamine (1.8 M, 505 mL, 0.91 mole) in THF (1.2 L) stirring at −60° C. under nitrogen. After stirring at −60° C. for 1 h, methyl 3-(4-fluorophenyl)-2-isobutyrylacrylate (175 g, 0.70 mole) was added over 75 min keeping the temperature below −50° C. The reaction was quenched with saturated ammonium chloride (750 mL) after the reaction had stirred at −60° C. for 35 min. After the reaction mixture had warmed to room temperature, ethyl acetate was added and the mixture transferred to a separatory funnel. The mixture was extracted with ethyl acetate (2×1 L). The combined organic layers were washed with 50% saturated ammonium chloride solution, water, and brine; dried over magnesium sulfate; and concentrated in vacuo to afford methyl 2-[(4-fluorophenyl)-(2-methoxy-3,4,5,6-tetrahydro-pyridin-3-yl)-methyl]-4-methyl-3-oxo-pentanoate (271 g).

출처