Potassium Carbonate → 7-[4-(4-(6-fluoro-benzisoxazolyl)-1-piperidinyl)-n-butoxy]-3,4-dihydro-2(1H)-quinolinone hydrochloride

HRID 241586Notes

Reaction equation

HRID 241586 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1.[F:18][C:19]1[CH:33]=[CH:32][C:22]2[C:23]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[N:24][O:25][C:21]=2[CH:20]=1.C(=O)([O-])[O-].[K+].[K+].Cl.CCO>C(O)C.CC(C)=O>[ClH:1].[F:18][C:19]1[CH:33]=[CH:32][C:22]2[C:23]([CH:26]3[CH2:27][CH2:28][N:29]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]4[CH:16]=[C:15]5[C:10]([CH2:11][CH2:12][C:13](=[O:17])[NH:14]5)=[CH:9][CH:8]=4)[CH2:30][CH2:31]3)=[N:24][O:25][C:21]=2[CH:20]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 104674677-(4-Chlorobutoxy)-1,2,3,4-tetrahydroquinolin-2-oneHCID 21887872Ethanol hydrochloride

Product 1

HCID 671807847-[4-(4-(6-fluoro-benzisoxazolyl)-1-piperidinyl)-n-butoxy]-3,4-dihydro-2(1H)-quinolinone hydrochlorideYield 42.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 702EthanolSolvent

Procedure

7-(4-chlorobutoxy)-3,4-dihydro-2(1H)-quinolinone (297 mg, 1 mmol), 4-(6-fluoro-1,2-benzisoxazolyl)-piperidine (242 mg, 1.1 mmol), and anhydrous potassium carbonate powder (414 mg, 3.3 mmol) are added to 10 ml and react at reflux for 24 hours. The reaction solution is evaporated to dryness and dispersed with 20 ml of dichloromethane and 20 ml of water respectively. The organic layer is extracted with water (20 ml×2) and saturated saline (20 ml) successively, dried over anhydrous magnesium sulfate, and evaporated to dryness to obtain a light yellow powder. The powder is dissolved with 5 ml of acetone and stirred in an ice bath. A white solid precipitates and is filtered, washed with small amount of acetone, and dried to obtain 260 mg of a whiter powder. The powder is dissolved in anhydrous ethanol and then thereto is drop-added HCl/EtOH to adjust to pH=2. A white deposit precipitates and is filtered out and recrystallized in anhydrous ethanol to obtain 200 mg of a product, with a yield of 42%.

Workup

  1. customreact
  2. temperatureat reflux for 24 hours
  3. customThe reaction solution is evaporated to dryness
  4. additiondispersed with 20 ml of dichloromethane and 20 ml of water respectively
  5. extractionThe organic layer is extracted with water (20 ml×2) and saturated saline (20 ml) successively
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated to dryness
  8. customto obtain a light yellow powder
  9. customA white solid precipitates
  10. filtrationis filtered
  11. washwashed with small amount of acetone
  12. customdried
  13. customto obtain 260 mg of a whiter powder
  14. customA white deposit precipitates
  15. filtrationis filtered out
  16. customrecrystallized in anhydrous ethanol

Sources & evidence

ORD record
ord-dd0e24e9802e4ee9af101b238bb24bb8
Source dataset
uspto-grants-2014_02
Patent number
US08653069B2

Reaction notes

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