反应详情

A mixture of 0.41 g of ethyl 6-amino-2,2-bis(fluoromethyl)-2H-1-benzopyran-4-carboxylate hydrochloride, 0.13 g of sulfuric acid, 0.10 g of sodium nitrite and 12 ml of H2O was stirred under ice-cooling for 1 hour. The reaction mixture was added dropwise to a mixture of 0.30 g of cuprous chloride and 10 ml of concentrated HCl under ice-cooling, then the mixture was stirred at room temperature for 3 hours followed by 3 hours at 70° C. with heating. Added 2N HCl to the reaction mixture and extracted with ethyl acetate. The resultant organic layer was washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. To the residue thus obtained added a mixture of 50 ml of ethyl alcohol and 2 ml of sulfuric acid and refluxed with heating for 2 hours. The reaction mixture was concentrated in vacuo to half a volume, added water to the residue and extracted with methylene chloride. The resultant organic layer was washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue thus obtained was purified with silica gel column chromatography (developing solution, ethyl acetate:hexane=1:10) to obtain 0.07 g of ethyl 6-chloro-2,2-bis(fluoromethyl)-2H-1-benzopyran-4-carboxylate with a melting point of 76°-78° C.

1. temperaturecooling for 1 hour
2. temperaturecooling
3. stirringthe mixture was stirred at room temperature for 3 hours
4. temperaturewith heating
5. extractionextracted with ethyl acetate
6. washThe resultant organic layer was washed with saturated sodium chloride solution
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customTo the residue thus obtained
10. additionadded
11. temperaturerefluxed
12. temperaturewith heating for 2 hours
13. concentrationThe reaction mixture was concentrated in vacuo to half a volume
14. additionadded water to the residue
15. extractionextracted with methylene chloride
16. washThe resultant organic layer was washed with saturated sodium chloride solution
17. dry with materialdried over sodium sulfate
18. concentrationconcentrated in vacuo
19. customThe residue thus obtained
20. customwas purified with silica gel column chromatography (developing solution, ethyl acetate:hexane=1:10)