تفاعل #10419

معادلة التفاعل

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

المردود 72.1%

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

المردود 72.1%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent is removed in vacuo
2. 2
   درجة الحرارةThe residue is cooled in an ice bath
3. 3
   أخرىtriturated with a saturated solution of sodium acetate in brine
4. 4
   أخرىThe precipitate is removed by filtration
5. 5
   غسيلwashed with the sodium acetate solution
6. 6
   أخرىdried in vacuo
7. 7
   غسيلThe dried precipitate is washed with ether
8. 8
   أخرىto remove
9. 9
   أخرىdried in vacuo
10. 10
    درجة الحرارةcooled 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
    أخرىthe bath is removed
14. 14
    workup.STIRRINGthe reaction is stirred to room temperature over 1 hour
15. 15
    أخرىThe solvent is removed in vacuo
16. 16
    workup.DISSOLUTIONthe residue is dissolved in water
17. 17
    درجة الحرارةcooled to 5° C.
18. 18
    أخرىThe resulting precipitate is removed by filtration
19. 19
    غسيلwashed with water
20. 20
    أخرىdried in vacuo

الإجراء التجريبي

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.

المصدر