tert-Butanol → Methyl{1-[4-(trifluoromethyl)benzyl]-5-[4-(trifluoromethyl)phenyl]pyrrolidin-3-yl}acetate

HRID 1869766ノート

反応式

HRID 1869766 の反応式
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:28]=[CH:27][C:6]([CH2:7][NH:8][CH:9]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[CH2:10]/[CH:11]=[CH:12]/[C:13]([O:15][CH3:16])=[O:14])=[CH:5][CH:4]=1.N1C2C=CC=C(CO)[C:34]=2N=N1.C(O)(C)(C)C.[I-].[I-].[Sm+2]>C1C=CC=CC=1>[CH3:16][O:15][C:13](=[O:14])[CH2:12][CH:11]1[CH2:10][CH:9]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:21][CH:22]=2)[N:8]([CH2:7][C:6]2[CH:27]=[CH:28][C:3]([C:2]([F:29])([F:30])[F:1])=[CH:4][CH:5]=2)[CH2:34]1

参加物

6

反応物 4

HCID 6386tert-ButanolHCID 57987371Methyl(2E)-5-{[4-(trifluoromethyl)benzyl]amino}-5-[4-(trifluoromethyl)phenyl]pent-2-enoateHCID 178506586HCID 178506586、化合物HCID 178519450HCID 178519450、化合物

生成物 1

HCID 76697410Methyl{1-[4-(trifluoromethyl)benzyl]-5-[4-(trifluoromethyl)phenyl]pyrrolidin-3-yl}acetate

試薬・触媒・溶媒 1

HCID 241Benzene溶媒

反応条件

温度
-78 °C

実験手順

The amine from Step 4 (400 mg, 0.9 mmol) was dissolved in benzene and benzotriazolemethanol (135 mg, 0.9 mmol) was added followed by powdered molecular sieves (470 mg). This was stirred overnight, the molecular sieves removed by filtration through Celite and the filtrate concentrated in vacuo. The residue was dissolved in THF (25 mL) and anhydrous t-butanol (0.17 mL, 0.9 mmol) was added. This solution was added dropwise via cannula onto a solution of samarium diiodide (27 mL, 2.7 mmol, 0.1M in THF) which was pre-cooled to −78° C. The mixture was stirred (−78° C. 0° C.) overnight then quenched with aq. K2CO3 and extracted with ethyl acetate. The organic extracts were washed with water, dried (MgSO4) and evaporated. The residue was purified on silica using 30-50% CH2Cl2 in iso-hexane to elute isomer a (245 mg) and isomer b (100 mg).

後処理

  1. customthe molecular sieves removed by filtration through Celite
  2. concentrationthe filtrate concentrated in vacuo
  3. dissolutionThe residue was dissolved in THF (25 mL)
  4. stirringThe mixture was stirred (−78° C. 0° C.) overnight
  5. customthen quenched with aq. K2CO3
  6. extractionextracted with ethyl acetate
  7. washThe organic extracts were washed with water
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was purified on silica using 30-50% CH2Cl2 in iso-hexane
  11. washto elute isomer a (245 mg) and isomer b (100 mg)

出典と根拠

ORDレコード
ord-e229d0757839427fa5623eceef026e93
出典データセット
uspto-grants-2009_12
特許番号
US07638629B2

反応ノート

読み込み中…