反応 #172112

反応方程式

methyl 2-(2-cyanovinyl)benzoate

Methyl 2-(2-cyanovinyl)benzoate

trifluoroacetic acid

N-Benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine

→

title compound

Trans-methyl 2-(1-benzyl-4-cyanopyrrolidin-3-yl)benzoate

溶媒

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   その他In a 50 mL round bottom flask were combined
2. 2
   workup.STIRRINGThe reaction was stirred at room temperature for 20 hours
3. 3
   その他quenched with aqueous sodium bicarbonate
4. 4
   抽出extracted with dichloromethane
5. 5
   洗浄washed with brine
6. 6
   乾燥dried over Na2SO4
7. 7
   ろ過filtered
8. 8
   その他the solvent was removed in vacuo
9. 9
   その他to provide the crude product
10. 10
    workup.ADDITIONThe mixture of isomers
11. 11
    workup.ADDITIONwas added to a silica gel column
12. 12
    洗浄was eluted with ethyl acetate/hexanes (gradient 0-20%, 40 minutes)

実験手順

In a 50 mL round bottom flask were combined methyl 2-(2-cyanovinyl)benzoate (Example 1A, 11.03 g, 58.9 mmol) trifluoroacetic acid (0.045 mL, 0.589 mmol) and dichloromethane (100 mL). N-Benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (64.8 mmol) was added as a solution in dichloromethane (100 mL) dropwise over 15 minutes while stirring under argon. The reaction was stirred at room temperature for 20 hours, then quenched with aqueous sodium bicarbonate and extracted with dichloromethane. The organic washes were combined and washed with brine, dried over Na2SO4, filtered, and the solvent was removed in vacuo to provide the crude product. The mixture of isomers was added to a silica gel column and was eluted with ethyl acetate/hexanes (gradient 0-20%, 40 minutes) to provide the title compound as the faster eluting (less polar) isomer. 1H NMR (500 MHz, CDCl3) δ ppm 2.82 (dd, 1H, J=9.09 Hz, J=7.81 Hz), 2.88 (dd, 1H, J=9.74 Hz, J=4.27 Hz), 2.99-3.03 (m, 1H), 3.05-3.09 (m, 1H), 3.29 (t, 1H, J=8.37 Hz), 3.71 (m, 2H), 3.94 (s, 3H), 4.51 (ddd, 1H, J=8.29 Hz, J=6.36 Hz, J=4.35 Hz), 7.25-7.40 (m, 6H), 7.50 (dt, 1H, J=7.65 Hz, J=1.45 Hz), 7.62 (d, 1H, J=7.24 Hz), 7.81 (dd, 1H, J=7.89 Hz, J=1.29 Hz); MS (DCI+) m/z 321.2 [M+H]+.

出典