반응 #69637

반응 방정식

Ethyl fluoroacetate

ethyl formate

Sodium hydride

acetamidine hydrochloride

sodium ethoxide

→

5-Fluoro-2-methylpyrimidin-4(3H)-one

수율 6.0%

용매

hexane

ethanol

반응 조건

후처리

1. 1
   기타to remove the mineral oil
2. 2
   기타dried
3. 3
   workup.ADDITIONadded to the stirring suspension
4. 4
   온도The reaction was slowly warmed to ambient temperature
5. 5
   기타The solvent was removed
6. 6
   workup.ADDITIONwere added to the reaction
7. 7
   온도by refluxing overnight
8. 8
   기타The ethanol was removed under reduced pressure
9. 9
   workup.DISSOLUTIONThe residue was dissolved in a minimum of water
10. 10
    추출The crude products were then extracted
11. 11
    세척washing exhaustively with 4:1 CHCl3/isopropanol
12. 12
    건조The combined organic phases were dried (MgSO4)
13. 13
    기타evaporated
14. 14
    기타The crude solid was purified by silica gel chromatography
15. 15
    세척eluting with 5-90% EtOAc/hexane

실험 절차

Sodium hydride (60%, 5.0 g, 125 mmol) was washed with hexane to remove the mineral oil and dried, then suspended in THF (50 mL) and cooled to 0° C. Ethyl fluoroacetate (13.30 g, 125 mmol) and ethyl formate (15.14 mL, 187 mmol) were mixed together and added to the stirring suspension. The reaction was slowly warmed to ambient temperature and stirred 3 days. The solvent was removed. A mixture of acetamidine hydrochloride (11.81 g, 125 mmol), sodium ethoxide (8.86 g, 125 mmol), and ethanol (60 mL) were added to the reaction followed by refluxing overnight. The ethanol was removed under reduced pressure. The residue was dissolved in a minimum of water and acidified to pH=6 with concentrated HCl. The crude products were then extracted by salting out from the aqueous phase and washing exhaustively with 4:1 CHCl3/isopropanol. The combined organic phases were dried (MgSO4) and evaporated. The crude solid was purified by silica gel chromatography eluting with 5-90% EtOAc/hexane to give 5-Fluoro-2-methylpyrimidin-4(3H)-one (44a, 0.95 g, 6%) as a white solid. Rf=0.08 (75% EtOAc/hexane). 1H NMR (400 MHz, DMSO-d6): δ 2.25 (d, J=1.0 Hz, 3H), 7.93 (d, J=3.8 Hz, 1H), 12.95 (br, 1H). LCMS 129.

출처