Potassium Carbonate → 8-(2-(7-Methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

HRID 39709Notes

Reaction equation

HRID 39709 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH3:14])=[CH:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.[H-].[Na+].CS(O[CH2:22][CH2:23][C:24]1([C:34]#[N:35])[CH2:33][CH2:32][C:27]2([O:31][CH2:30][CH2:29][O:28]2)[CH2:26][CH2:25]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH3:14])=[CH:8][C:9](=[O:13])[N:10]2[CH2:22][CH2:23][C:24]2([C:34]#[N:35])[CH2:33][CH2:32][C:27]3([O:28][CH2:29][CH2:30][O:31]3)[CH2:26][CH2:25]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydride2×HCID 7615487-Methoxy-4-methylquinolin-2-olHCID 866431842-(8-Cyano-1,4-dioxaspiro[4.5]decan-8-yl)ethyl methanesulfonate

Product 1

HCID 675403228-(2-(7-Methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 10 mL of an N,N-dimethylformamide suspension containing 0.63 g of 7-methoxy-4-methylquinolin-2(1H)-one, 0.17 g of 60% sodium hydride at 55° C., and the mixture was stirred at the same temperature for 35 minutes. Thereto was added dropwise 8 mL of an N,N-dimethylformamide solution containing 0.99 g of 2-(8-cyano-1,4-dioxaspiro[4.5]decan-8-yl)ethyl methanesulfonate at 50° C., and the mixture was stirred at 50 to 55° C. for 2 hours and 50 minutes. Thereto was added 53 mg of 60% sodium hydride at the same temperature, and after further stirring for 3 hours, the mixture was added with 0.46 g of potassium carbonate at the same temperature, and further stirred for 3 hours. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were 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 30:70] to obtain 200 mg g of a white solid, 8-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile.

Workup

  1. stirringthe mixture was stirred at 50 to 55° C. for 2 hours and 50 minutes
  2. stirringafter further stirring for 3 hours
  3. stirringfurther stirred for 3 hours
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washthe resultant solution was washed with an aqueous saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by flash silica gel column chromatography [hexane: gradient elution of ethyl acetate 30:70]

Sources & evidence

ORD record
ord-bd621c67675747a7bdd26208626bc37b
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Reaction notes

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