N-(2,2-difluoroethylidene)-4-methoxyaniline → Tert-butyl 5-chloro-2-{3,3-difluoro-2-[(4-methoxyphenyl)amino]propyl}benzylcarbamate

HRID 1058244노트

반응식

HRID 1058244 반응식
C([Li])(CC)C.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([CH3:22])=[C:11]([CH:21]=1)[CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].[F:23][CH:24]([F:35])[CH:25]=[N:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>C1COCC1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:22][CH:25]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH:24]([F:35])[F:23])=[C:11]([CH:21]=1)[CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19]

참가 물질

5

반응물 3

HCID 10397509N-(2,2-difluoroethylidene)-4-methoxyanilineHCID 18672379Tert-butyl 5-chloro-2-methylbenzylcarbamateHCID 178418400CID 53628100

생성물 1

HCID 18672390Tert-butyl 5-chloro-2-{3,3-difluoro-2-[(4-methoxyphenyl)amino]propyl}benzylcarbamate수율 16.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

sec-Butyl-lithium (1.3 M in cyclohexane, 10.72 mL) was added to a stirred solution of tert-butyl 5-chloro-2-methylbenzylcarbamate (1.781 g, 6.96 mmol) in THF (14 mL) at −78° C. under nitrogen to give a deep red solution. After 10 min N-(-2,2-difluoroethylidene)-N-(4-methoxyphenyl)amine (1.29 g, 6.96 mmol) was added and after a further 5 min the solution was quenched with excess saturated aqueous NH4Cl and warmed to ambient temperature. The solution was partitioned between EtOAc and brine. The organic layer was dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 5-15% ethyl acetate/hexanes gradient) to give tert-butyl 5-chloro-2-{3,3-difluoro-2-[(4-methoxyphenyl)amino]propyl}benzylcarbamate (0.516 g) as a foam; MS m/z=441.1.

후처리

  1. customto give a deep red solution
  2. customwas quenched with excess saturated aqueous NH4Cl
  3. customThe solution was partitioned between EtOAc and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 5-15% ethyl acetate/hexanes gradient)

출처 및 근거

ORD 기록
ord-5f761db51de9400dbbb0c38f05c5f1f5
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06515011B2

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