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

HRID 1058244Notes

Reaction equation

HRID 1058244 reaction equation
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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-5f761db51de9400dbbb0c38f05c5f1f5
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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