Water → Ethyl 1-[2,4-bis(trifluoromethyl)benzyl]-7-oxoazepane-4-carboxylate

HRID 1620633Notes

Reaction equation

HRID 1620633 reaction equation
[O:1]=[C:2]1[NH:8][CH2:7][CH2:6][CH:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.[H-].[Na+].Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=1[C:28]([F:31])([F:30])[F:29].O>C1COCC1>[F:29][C:28]([F:30])([F:31])[C:19]1[CH:20]=[C:21]([C:24]([F:27])([F:25])[F:26])[CH:22]=[CH:23][C:18]=1[CH2:17][N:8]1[C:2](=[O:1])[CH2:3][CH2:4][CH:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5188712,4-Bis(trifluoromethyl)benzyl bromideHCID 23093698Ethyl 7-oxoazepane-4-carboxylate

Product 1

HCID 86678800Ethyl 1-[2,4-bis(trifluoromethyl)benzyl]-7-oxoazepane-4-carboxylateYield 68.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 7-oxoazepane-4-carboxylate (9.78 g) in THF (250 mL) was added 60% sodium hydride (2.33 g, containing mineral oil) under ice-cooling. The reaction mixture was stirred for 5 min under ice-cooling, and 1-(bromomethyl)-2,4-bis(trifluoromethyl)benzene (17.9 g) was added. The reaction mixture was stirred at room temperature overnight, water was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (14.9 g).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-d8b1d17594cd4951af388d45bcd432dd
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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