반응 #10419

반응 방정식

5,6-difluoro-2-methyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

chlorosulfonyl isocyanate

sodium acetate

sodium tert-butoxide

→

title compound

수율 72.1%

8,9-Difluoro-5-methyl-6,7-dihydro-5H-pyrido[3,2,1-ij]quinazoline-1,3-dione

수율 72.1%

용매

dichloromethane

반응 조건

후처리

1. 1
   기타the solvent is removed in vacuo
2. 2
   온도The residue is cooled in an ice bath
3. 3
   기타triturated with a saturated solution of sodium acetate in brine
4. 4
   기타The precipitate is removed by filtration
5. 5
   세척washed with the sodium acetate solution
6. 6
   기타dried in vacuo
7. 7
   세척The dried precipitate is washed with ether
8. 8
   기타to remove
9. 9
   기타dried in vacuo
10. 10
    온도cooled to 5° C.
11. 11
    workup.ADDITIONAfter the addition
12. 12
    workup.STIRRINGthe reaction mixture is stirred at 5° C. for 30 minutes
13. 13
    기타the bath is removed
14. 14
    workup.STIRRINGthe reaction is stirred to room temperature over 1 hour
15. 15
    기타The solvent is removed in vacuo
16. 16
    workup.DISSOLUTIONthe residue is dissolved in water
17. 17
    온도cooled to 5° C.
18. 18
    기타The resulting precipitate is removed by filtration
19. 19
    세척washed with water
20. 20
    기타dried in vacuo

실험 절차

A solution of 1.07 g (4.4 mmol) of 5,6-difluoro-2-methyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (Example 32) in 25 mL of dichloromethane is cooled to −20° C. and treated dropwise with 0.85 g (6.0 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at −20° C. for 1 hour, treated with 1.0 g (12 mmol) of solid sodium acetate, and the solvent is removed in vacuo. The residue is cooled in an ice bath and triturated with a saturated solution of sodium acetate in brine. The precipitate is removed by filtration, washed with the sodium acetate solution and dried in vacuo. The dried precipitate is washed with ether to remove starting material and dried in vacuo. The dried solid is suspended in 40 mL of dry tetrahydrofuran, cooled to 5° C. and treated portionwise with 1.2 g (12 mmol) of sodium tert-butoxide. After the addition is complete, the reaction mixture is stirred at 5° C. for 30 minutes, the bath is removed, and the reaction is stirred to room temperature over 1 hour. The solvent is removed in vacuo; the residue is dissolved in water, cooled to 5° C. and acidified with formic acid. The resulting precipitate is removed by filtration, washed with water and dried in vacuo affording 0.8 g of the title compound, mp 212–214° C.

출처