Water → 6-Cyano-4-(1H-indol-5-yloxy)-7-[(1-(t-butoxycarbonyloxy)piperidin-4-yl)methyloxy]quinoline

HRID 387875Notes

Reaction equation

HRID 387875 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[OH:13])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]=[CH:18]2)#[N:2].[C:24](=[O:27])([O-:26])[O-:25].[K+].[K+].Br[CH2:31][CH:32]1[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]1.O>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([O:27][C:24]([O:26][C:3]([CH3:4])([CH3:12])[CH3:1])=[O:25])[CH2:34][CH2:33]1)[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]=[CH:18]2)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 1358293896-Cyano-4-(1H-indol-5-yloxy)-7-hydroxyquinoline

Product 1

HCID 672017656-Cyano-4-(1H-indol-5-yloxy)-7-[(1-(t-butoxycarbonyloxy)piperidin-4-yl)methyloxy]quinolineYield 118.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

After dissolving 6-cyano-4-(1H-indol-5-yloxy)-7-hydroxyquinoline (1.72 g, 5.7084 mmol) in N,N-dimethylformamide (20 ml), there were added potassium carbonate (0.87 g, 6.2792 mmol) and tert-butyl 4-bromomethylpiperidine-1-carboxylate (1.75 g, 6.2792 mmol), and the mixture was heated and stirred at 70° C. for 7 hours. After allowing it to cool to room temperature, water was added, extraction was performed with ethyl acetate and tetrahydrofuran, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure, after which the residue was adsorbed onto silica gel. Purification was performed by silica gel column chromatography (hexane/ethyl acetate system), and then ethyl acetate/ethanol/hexane was added to the obtained yellow oil to precipitate crystals. The crystals were filtered out, washed with hexane:ethanol=10:1 and dried by aspiration to obtain the title compound (1.786 g, 3.3852 mmol, 59.30%) as light yellow crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto cool to room temperature
  3. extractionextraction
  4. washthe extract was washed with saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customPurification
  8. additionethyl acetate/ethanol/hexane was added to the obtained yellow oil
  9. customto precipitate crystals
  10. filtrationThe crystals were filtered out
  11. washwashed with hexane
  12. dry with materialethanol=10:1 and dried by aspiration

Sources & evidence

ORD record
ord-24b74fa3e24040ffb7c705ad926e29c2
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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