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Lithium Hexamethyldisilazide → 2,6-Difluoro-N-(1-{[5-(phenyloxy)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

HRID 1946402
ノート
印刷プレビュー

反応式

HRID 1946402 の反応式
[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][NH:9][N:8]=1)=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:28][C:29]1[CH:34]=[C:33]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=[CH:31][C:30]=1[C:42]([F:45])([F:44])[F:43]>C1COCC1>[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:28][C:29]2[CH:34]=[C:33]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:32]=[CH:31][C:30]=2[C:42]([F:43])([F:44])[F:45])[N:8]=1)=[O:5]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 667707242-(Bromomethyl)-4-(phenyloxy)-1-(trifluoromethyl)benzeneHCID 178522346HCID 178522346、化合物2 回

生成物 1

HCID 595478692,6-Difluoro-N-(1-{[5-(phenyloxy)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a stirred solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(100 mg, 0.448 mmol) in dry THF (6.0 ml) under nitrogen at ambient temperature was added 1.0 M lithium bis(trimethylsilyl)amide (0.45 ml, 0.45 mmol) dropwise and then the solution stirred for approximately 30 min. To the solution was added a solution of crude 2-(bromomethyl)-4-(phenyloxy)-1-(trifluoromethyl)benzene (0.135 g) in dry THF (2.5 ml) and stirred for 7 h. The solvent was removed using a stream of nitrogen. To the residue was added saturated aqueous sodium bicarbonate (approximately 7 ml) and then the residue extracted three times with chloroform. The combined organic extracts were filtered through a hydrophobic frit. The solvent was removed in vacuo and the residue purified on MDAP (Method B). The appropriate fractions were combined and solvent evaporated in vacuo. The residue was dried under high vacuum at 45° C. to give the title compound as a white solid (85 mg); LCMS: (System 4) MH+=474, tRET=3.30 min.

後処理

  1. customat ambient temperature
  2. stirringstirred for 7 h
  3. customThe solvent was removed
  4. additionTo the residue was added saturated aqueous sodium bicarbonate (approximately 7 ml)
  5. extractionthe residue extracted three times with chloroform
  6. filtrationThe combined organic extracts were filtered through a hydrophobic frit
  7. customThe solvent was removed in vacuo
  8. customthe residue purified on MDAP (Method B)
  9. customsolvent evaporated in vacuo
  10. customThe residue was dried under high vacuum at 45° C.

出典と根拠

ORDレコード
ord-51eccecd87944105b67db458dbcb9371
出典データセット
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08399436B2

反応ノート

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