Reaction #67987

Reaction equation

sodium hydride

7-methoxy-4-methylquinolin-2(1H)-one

sodium hydride

potassium carbonate

2-(8-cyano-1,4-dioxaspiro[4.5]decan-8-yl)ethyl methanesulfonate

→

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

Solvents

N,N-dimethylformamide

ethyl acetate

water

N,N-dimethylformamide

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred at 50 to 55° C. for 2 hours and 50 minutes
2. 2
   workup.STIRRINGafter further stirring for 3 hours
3. 3
   workup.STIRRINGfurther stirred for 3 hours
4. 4
   OtherThe organic layer was separated
5. 5
   Extractionthe aqueous layer was extracted with ethyl acetate
6. 6
   Washthe resultant solution was washed with an aqueous saturated sodium chloride solution
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Otherthe solvent was removed under reduced pressure
9. 9
   OtherThe residue thus obtained
10. 10
    Otherwas purified by flash silica gel column chromatography [hexane: gradient elution of ethyl acetate 30:70]

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.

Source