Ethyl formate → 5-Fluoro-2-methylpyrimidin-4-ol

HRID 41359노트

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HRID 41359 반응식
[H-].[Na+].[F:3][CH2:4][C:5]([O:7]CC)=O.[CH:10](OCC)=O.Cl.[C:16]([NH2:19])(=[NH:18])[CH3:17].[O-]CC.[Na+]>CCCCCC.C(O)C>[F:3][C:4]1[C:5](=[O:7])[NH:18][C:16]([CH3:17])=[N:19][CH:10]=1

참가 물질

8

반응물 5

HCID 8025Ethyl formateHCID 9988Ethyl fluoroacetateHCID 24758Sodium hydrideHCID 67170Acetamidine monohydrochlorideHCID 2723922Sodium ethoxide

생성물 1

HCID 450805255-Fluoro-2-methylpyrimidin-4-ol수율 6%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8058Hexane용매

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온도
0 °C

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.

후처리

  1. customto remove the mineral oil
  2. customdried
  3. additionadded to the stirring suspension
  4. temperatureThe reaction was slowly warmed to ambient temperature
  5. customThe solvent was removed
  6. additionwere added to the reaction
  7. temperatureby refluxing overnight
  8. customThe ethanol was removed under reduced pressure
  9. dissolutionThe residue was dissolved in a minimum of water
  10. extractionThe crude products were then extracted
  11. washwashing exhaustively with 4:1 CHCl3/isopropanol
  12. dry with materialThe combined organic phases were dried (MgSO4)
  13. customevaporated
  14. customThe crude solid was purified by silica gel chromatography
  15. washeluting with 5-90% EtOAc/hexane

출처 및 근거

ORD 기록
ord-ec9a834be1d84357aee56b2d10bc5232
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530652B2

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