Dimethylformamide → 1-(2-(1,4-Dioxaspiro[4.5]decan-8-yl)ethyl)-7-methoxy-4-methylquinolin-2(1h)-one

HRID 2193074Notes

Reaction equation

HRID 2193074 reaction equation
CN(C)C=O.[CH3:6][O:7][C:8]1[CH:17]=[C:16]2[C:11]([C:12]([CH3:19])=[CH:13][C:14](=[O:18])[NH:15]2)=[CH:10][CH:9]=1.[H-].[Na+].CS(O[CH2:27][CH2:28][CH:29]1[CH2:38][CH2:37][C:32]2([O:36][CH2:35][CH2:34][O:33]2)[CH2:31][CH2:30]1)(=O)=O>C(OCC)(=O)C.O>[O:33]1[C:32]2([CH2:31][CH2:30][CH:29]([CH2:28][CH2:27][N:15]3[C:16]4[C:11](=[CH:10][CH:9]=[C:8]([O:7][CH3:6])[CH:17]=4)[C:12]([CH3:19])=[CH:13][C:14]3=[O:18])[CH2:38][CH2:37]2)[O:36][CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydride2×HCID 7615487-Methoxy-4-methylquinolin-2-olHCID 578925572-(1,4-Dioxaspiro[4.5]decan-8-yl)ethyl methanesulfonate

Product 1

HCID 593979561-(2-(1,4-Dioxaspiro[4.5]decan-8-yl)ethyl)-7-methoxy-4-methylquinolin-2(1h)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
62.5 °C

Procedure

To 3 mL of an N,N-dimethylformamide solution containing 0.12 g of 7-methoxy-4-methylquinolin-2(1H)-one, 28 mg of a 60% aqueous sodium hydride solution was added at 50° C., and the mixture was stirred at 60 to 65° C. for 30 minutes. Thereto was added 2 mL of an N,N-dimethylformamide solution containing 0.18 g of 2-(1,4-dioxaspiro[4.5]decan-8-yl)ethyl methanesulfonate at 50° C., and the mixture was stirred at 60 to 65° C. for 1 hour and 20 minutes. Thereto was added 14 mg of a 60% aqueous sodium hydride solution at the same temperature, and the mixture was stirred for 1 hour and 45 minutes. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were then added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=40:60 to 30:70] to obtain 65 mg of a colorless oily substance, 1-(2-(1,4-dioxaspiro[4.5]decan-8-yl)ethyl)-7-methoxy-4-methylquinolin-2(1H)-one.

Workup

  1. additionwas added at 50° C.
  2. stirringthe mixture was stirred at 60 to 65° C. for 1 hour and 20 minutes
  3. stirringthe mixture was stirred for 1 hour and 45 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washthe resultant solution was washed with an aqueous saturated sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customThe residue thus obtained
  11. customwas purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=40:60 to 30:70]

Sources & evidence

ORD record
ord-d9fb4b71f95a4df8a242b58fc2a6f19f
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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