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

HRID 1887556

반응식

HRID 1887556 반응식
[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]

참가 물질

10

반응물 6

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b47f05ddeaaf4fba8fa7c0a0068baccf
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501756B2

연결된 노트

불러오는 중…