反応 #69637

反応方程式

Ethyl fluoroacetate

ethyl formate

Sodium hydride

acetamidine hydrochloride

sodium ethoxide

→

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

収率 6.0%

溶媒

hexane

ethanol

反応条件

後処理

1. 1
   その他to remove the mineral oil
2. 2
   その他dried
3. 3
   workup.ADDITIONadded to the stirring suspension
4. 4
   温度The reaction was slowly warmed to ambient temperature
5. 5
   その他The solvent was removed
6. 6
   workup.ADDITIONwere added to the reaction
7. 7
   温度by refluxing overnight
8. 8
   その他The ethanol was removed under reduced pressure
9. 9
   workup.DISSOLUTIONThe residue was dissolved in a minimum of water
10. 10
    抽出The crude products were then extracted
11. 11
    洗浄washing exhaustively with 4:1 CHCl3/isopropanol
12. 12
    乾燥The combined organic phases were dried (MgSO4)
13. 13
    その他evaporated
14. 14
    その他The crude solid was purified by silica gel chromatography
15. 15
    洗浄eluting with 5-90% EtOAc/hexane

実験手順

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.

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