Potassium Carbonate → cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide

HRID 659231

Reaction equation

HRID 659231 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21521Bis(2-bromoethyl) etherHCID 58062952cis-N-(2-amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide2×

Product 1

HCID 58062968cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamideYield 68.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with 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/methanol/ammonia 100:0:0→140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m/e=403.3 [(M+H)+].

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. customThe solvent was evaporated off
  3. extractionethyl acetate and was extracted three times with 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/methanol/ammonia 100:0:0→140:10:1)

Sources & evidence

ORD record
ord-f0629f05d65d4bbb8f95d39f560479e8
Source dataset
uspto-grants-2011_12
Patent number
US08080541B2

Linked notes

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