Potassium Carbonate → 2,4-Bis(trifluoromethyl)benzamide

HRID 1950900

Reaction equation

HRID 1950900 reaction equation
N[C@H]1CCCC[C@H]1[NH:8][C:9](=[O:26])[C:10]1[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][C:13]([C:20]([F:23])([F:22])[F:21])=[CH:12][C:11]=1OC.C(=O)([O-])[O-].[K+].[K+].[I-].C([N+]1(C)CCC(=O)CC1)C>C(O)C>[F:21][C:20]([F:22])([F:23])[C:13]1[CH:14]=[C:15]([C:16]([F:19])([F:17])[F:18])[C:10]([C:9]([NH2:8])=[O:26])=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 110975681-Ethyl-1-methyl-4-oxopiperidin-1-ium iodideHCID 58062915cis-N-(2-Amino-cyclohexyl)-2-methoxy-4,6-bis-trifluoromethyl-benzamide2×

Product 1

HCID 27360992,4-Bis(trifluoromethyl)benzamideYield 120%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

cis-N-(2-Amino-cyclohexyl)-2-methoxy-4,6-bis-trifluoromethyl-benzamide (intermediate H) (400 mg, 1.04 mmol) was dissolved in 27 mL ethanol. Potassium carbonate (86 mg, 0.062 mmol) and 1-ethyl-1-methyl-4-oxo-piperidinium iodide (420 mg, 1.56 mmol) were added. The reaction mixture was refluxed for 2 h. The solvent was evaporated off. The residue was extracted with saturated sodium bicarbonate solution and ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/ethyl acetate 1:0->1:1) yielded cis 2-methoxy-N-2-(4-oxo-piperidin-1-yl)-cyclohexyl]-4,6-bis-trifluoromethyl-benzamide as a light yellow solid (321 mg, 66%), MS: m/e=467.2 [(M+H)+].

Workup

  1. temperatureThe reaction mixture was refluxed for 2 h
  2. customThe solvent was evaporated off
  3. extractionThe residue was extracted with saturated sodium bicarbonate solution and ethyl acetate
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (dichloromethane/ethyl acetate 1:0->1:1)

Sources & evidence

ORD record
ord-2fc3b3e3aa674781b526b6bf02b76ee4
Source dataset
uspto-grants-2013_03
Patent number
US08404673B2

Linked notes

Loading…