Water → HCID 178429116, compound

HRID 384480Notes

Reaction equation

HRID 384480 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:19][O:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]2)[C:10]=1[CH3:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:30][CH2:31][CH2:32][C:33](Cl)=[O:34].C(N(CC)CC)C.O>ClCCl>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:19][O:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([N:27]3[CH2:30][CH2:31][CH2:32][C:33]3=[O:34])[CH2:23][CH2:22]2)[C:10]=1[CH3:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 702254-Bromobutyryl chlorideHCID 178429117HCID 178429117, compound

Product 1

HCID 178429116HCID 178429116, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of trans-4-{[4-(benzyloxy)-3-methylquinolin-2-yl]methoxy}cyclohexaneamine (300 mg) in dichloromethane (5 mL) were added 4-bromo butanoic acid chloride (0.11 mL) and triethylamine (0.15 mL) under ice-cooling, followed by stirring at the same temperature for 45 minutes. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was dissolved in THF, and 60% sodium hydride (50 mg) was added thereto. The reaction mixture was stirred at room temperature for 2 hours, followed by stirring for another 15 hours while heating it in an oil bath at 60° C. 60% sodium hydride (50 mg) was added to the reaction mixture, followed by stirring for 4 hours while heating it in an oil bath at 60° C. The reaction mixture was cooled to room temperature, and water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: chloroform/methanol=100/0˜95/5). The solvent was evaporated under reduced pressure, and the residue was then dried under vacuum at room temperature to obtain 161 mg of 1-(trans-4-{[4-(benzyloxy)-3-methylquinolin-2-yl]methoxy}cyclohexyl)pyrrolidin-2-one as a yellow oily substance.

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with chloroform
  3. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in THF
  7. addition60% sodium hydride (50 mg) was added
  8. stirringThe reaction mixture was stirred at room temperature for 2 hours
  9. stirringby stirring for another 15 hours
  10. addition60% sodium hydride (50 mg) was added to the reaction mixture
  11. stirringby stirring for 4 hours
  12. temperaturewhile heating it in an oil bath at 60° C
  13. temperatureThe reaction mixture was cooled to room temperature
  14. additionwater was then added
  15. extractionfollowed by extraction with ethyl acetate
  16. washThe organic layer was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. customthe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=100/0˜95/5)
  20. customThe solvent was evaporated under reduced pressure
  21. customthe residue was then dried under vacuum at room temperature

Sources & evidence

ORD record
ord-2bf4ce50a2974f608b30e56b2de8bfbf
Source dataset
uspto-grants-2013_02
Patent number
US08367702B2

Reaction notes

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