Imidazole → 3-(tert-Butyl-dimethyl-silanyloxymethyl)-5-trifluoromethyl-phenylamine

HRID 45061

反応式

HRID 45061 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)C(O)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3].[F-].[Na+].N1C=CN=[CH:24]1.[CH3:28][C:29]([Si:32](Cl)(C)C)([CH3:31])[CH3:30].CCO[C:39]([CH3:41])=[O:40]>C1COCC1.C(Cl)Cl.O>[C:29]([SiH2:32][O:40][C:39]([CH3:41])([CH3:24])[C:4]1[CH:3]=[C:2]([NH2:1])[CH:10]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:8]=1)([CH3:31])([CH3:30])[CH3:28]

参加物

10

反応物 6

HCID 795ImidazoleHCID 5235Sodium FluorideHCID 8857Ethyl AcetateHCID 28928tert-Butyldimethylsilyl chlorideHCID 6095563-Amino-5-(trifluoromethyl)benzoic acidHCID 21226445Aluminium lithium hydride

生成物 1

HCID 1373297753-(tert-Butyl-dimethyl-silanyloxymethyl)-5-trifluoromethyl-phenylamine

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 3-Amino-5-trifluoromethyl-benzoic acid (2.0 g, 9.76 mmol) in THF (40 mL) at 0° C. is added LiAlH4 in THF (1 M, 39 mL). The mixture is warmed to reflux and stirred for 62 h. The mixture is then cooled to 0° C. and NaF (2.2 g) is added followed by H2O (3.8 mL). The slurry is stirred for 10 minutes and then allowed to warm to rt and stir an additional 40 min. The mixture is filtered and the solid is rinsed with EtOAc and MeOH. The filtrate is concentrated and the crude residue is mixed with imidazole (2.66 g, 39 mmol) and DCM (30 mL) at 0° C. TBSCl (3.5 g, 23.4 mmol) is added and the mixture is stirred at rt for 5 h. The reaction mixture is then diluted with EtOAc, washed with saturated aqueous NaHCO3, brine, and dried over Na2SO4. Concentration provides the title compound that is carried on to next step without further purification. MS (ESI) m/z 306.1 (M+1).

後処理

  1. temperatureThe mixture is warmed
  2. temperatureto reflux
  3. stirringThe slurry is stirred for 10 minutes
  4. temperatureto warm to rt
  5. stirringstir an additional 40 min
  6. filtrationThe mixture is filtered
  7. washthe solid is rinsed with EtOAc and MeOH
  8. concentrationThe filtrate is concentrated
  9. stirringthe mixture is stirred at rt for 5 h
  10. washwashed with saturated aqueous NaHCO3, brine
  11. dry with materialdried over Na2SO4
  12. concentrationConcentration

出典と根拠

ORDレコード
ord-1875c82f897145ed8ba3994b007c15ee
出典データセット
uspto-grants-2013_09
特許番号
US08541432B2

関連ノート

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