反应详情

A mixture of (E)-4-methoxy-but-3-en-2-one (20 mmol) and ethyl difluoroacetate (24 mmol) is added dropwise to a mixture of potassium tert-butoxide (26 mmol) and diethyl ether (50 ml) under nitrogen atmosphere at −15° C. over 30 min. The mixture is allowed to warm up to room temperature slowly over 3 h. After cooling to 0° C., acetic acid (26 mmol) and H2O (10 ml) are successively added dropwise to the reaction mixture. The organic layer is separated, washed with sat. aq. NaHCO3, dried over MgSO4, and evaporated in vacuo. The residue is dissolved in i-propanol (30 ml). To the solution, conc. HCl (2 ml) is added and the mixture is refluxed for 3 h. After cooling, the reaction mixture is neutralised with sat. aq. NaHCO3 and extracted with CH2Cl2. The organic layer is dried over MgSO4 and evaporated in vacuo. The residue is dissolved in i-propanol (20 ml). To the solution, 28% aq. NH3 (50 mmol) is added and the mixture is refluxed for 20 h. After cooling, the reaction mixture is diluted with H2O and extracted with AcOEt. The organic layer is dried over MgSO4 and evaporated in vacuo. The residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:1) to give 2-difluoromethyl-pyridin-4-ol in 32% yield.

1. temperatureAfter cooling to 0° C.
2. customThe organic layer is separated
3. washwashed with sat. aq. NaHCO3
4. dry with materialdried over MgSO4
5. customevaporated in vacuo
6. dissolutionThe residue is dissolved in i-propanol (30 ml)
7. additionTo the solution, conc. HCl (2 ml) is added
8. temperaturethe mixture is refluxed for 3 h
9. temperatureAfter cooling
10. extractionextracted with CH2Cl2
11. dry with materialThe organic layer is dried over MgSO4
12. customevaporated in vacuo
13. dissolutionThe residue is dissolved in i-propanol (20 ml)
14. temperaturethe mixture is refluxed for 20 h
15. temperatureAfter cooling
16. extractionextracted with AcOEt
17. dry with materialThe organic layer is dried over MgSO4
18. customevaporated in vacuo
19. customThe residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:1)