反应详情

温度

-20 °C

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.

1. customthe solvent is removed in vacuo
2. temperatureThe residue is cooled in an ice bath
3. customtriturated with a saturated solution of sodium acetate in brine
4. customThe precipitate is removed by filtration
5. washwashed with the sodium acetate solution
6. customdried in vacuo
7. washThe dried precipitate is washed with ether
8. customto remove
9. customdried in vacuo
10. temperaturecooled to 5° C.
11. additionAfter the addition
12. stirringthe reaction mixture is stirred at 5° C. for 30 minutes
13. customthe bath is removed
14. stirringthe reaction is stirred to room temperature over 1 hour
15. customThe solvent is removed in vacuo
16. dissolutionthe residue is dissolved in water
17. temperaturecooled to 5° C.
18. customThe resulting precipitate is removed by filtration
19. washwashed with water
20. customdried in vacuo