Water → HCID 86713976, compound

HRID 514253Notes

Reaction equation

HRID 514253 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11](=[O:28])[NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:14]([F:17])([F:16])[F:15])[NH:8]2)=[CH:4][C:3]=1[CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34].[H-].[Na+].I[CH2:41][CH3:42].O>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11](=[O:28])[NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=3)[C:14]([F:16])([F:17])[F:15])[N:8]2[CH2:41][CH3:42])=[CH:4][C:3]=1[CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 86713974HCID 86713974, compound

Product 1

HCID 86713976HCID 86713976, compoundYield 60.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl {[6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indol-5-yl]methyl}carbamate (90% pure; 0.74 g, 1.21 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (12.5 ml). Sodium hydride (60%; 0.053 g, 1.33 mmol) was added and the mixture was stirred while cooling with ice for 2 h. Subsequently, iodoethane (0.19 g, 1.21 mmol) was added dropwise. The reaction mixture was thawed while stirring within 16 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (4/1) and gave 0.42 g (60% of theory) of tert-butyl {[6-chloro-1-ethyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indol-5-yl]methyl}carbamate.

Workup

  1. temperaturewhile cooling with ice for 2 h
  2. stirringwhile stirring within 16 h
  3. customthe phases were separated
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was chromatographed with cyclohexane/ethyl acetate (4/1)

Sources & evidence

ORD record
ord-c601e5de05d346fa8e6cae0b31af03fe
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Reaction notes

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