Trifluoroacetic acid → trans-Methyl 2-(1-benzyl-4-cyanopyrrolidin-3-yl)benzoate

HRID 84930

反応式

HRID 84930 の反応式
[C:1]([CH:3]=[CH:4][C:5]1[CH:14]=[CH:13][CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])#[N:2].FC(F)(F)C(O)=O.[CH2:22]([N:29]([CH2:33][Si](C)(C)C)[CH2:30]OC)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>ClCCl>[CH2:22]([N:29]1[CH2:30][C@@H:3]([C:1]#[N:2])[C@H:4]([C:5]2[CH:14]=[CH:13][CH:12]=[CH:11][C:6]=2[C:7]([O:9][CH3:10])=[O:8])[CH2:33]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 66818837Methyl 2-(2-cyanovinyl)benzoate

生成物 1

HCID 131731901trans-Methyl 2-(1-benzyl-4-cyanopyrrolidin-3-yl)benzoate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

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]+.

後処理

  1. customIn a 50 mL round bottom flask were combined
  2. stirringThe reaction was stirred at room temperature for 20 hours
  3. customquenched with aqueous sodium bicarbonate
  4. extractionextracted with dichloromethane
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo
  9. customto provide the crude product
  10. additionThe mixture of isomers
  11. additionwas added to a silica gel column
  12. washwas eluted with ethyl acetate/hexanes (gradient 0-20%, 40 minutes)

出典と根拠

ORDレコード
ord-6e7b1db78c4c4e8397cfa597d1e7a459
出典データセット
uspto-grants-2014_09
特許番号
US08846951B2

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