Ethyl formate → 5-(2,4-Difluorophenoxy)-2-methylsulfanylpyrimidin-4-ol

HRID 518359

반응식

HRID 518359 반응식
C([O:3][C:4](=O)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14])C.C(OCC)=O.[H-].[Na+].[O-]CC.[Na+].S(O)(O)(=O)=O.[CH3:32][S:33][C:34](=[NH:36])[NH2:35].[CH3:37]SC(=N)N>C1COCC1.CCO>[F:14][C:8]1[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=1[O:6][C:5]1[C:4]([OH:3])=[N:36][C:34]([S:33][CH3:32])=[N:35][CH:37]=1

참가 물질

8

반응물 5

HCID 8025Ethyl formateHCID 13347Bis(S-methylisothiouronium) sulfateHCID 24758Sodium hydrideHCID 2723922Sodium ethoxideHCID 4506666Ethyl 2-(2,4-difluorophenoxy)acetate

생성물 1

HCID 1785034745-(2,4-Difluorophenoxy)-2-methylsulfanylpyrimidin-4-ol수율 60%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 2-(2,4-difluorophenoxyl)acetic acid ethyl ester (8.0 g, 37.01 mmol) and ethyl formate (4.11 g, 55.51 mmol) in dry THF (200 mL) was added NaH (1.55 g, 38.75 mmol) slowly at 0° C. The mixture was then refluxed for 2 h. In a separate flask, sodium ethoxide (3.02 g, 44.41 mmol) and S-methylthiopseudourea hemisulfate (6.17 g, 44.41 mmol) in EtOH (100 mL) were stirred at 20° C. for 2 h and then the resulting mixture was added to the above THF solution. The combined mixture was refluxed for 12 h. After concentration under vacuum, water (20 mL) and HCl (10 mL, aq. 1N) were added. The suspended solids were collected and washed with water (50 mL×3) and EtOH (50 mL×3) and dried to give the title compound (6.0 g, 60.0% yield) as a light yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 7.84 (s, 1H), 7.42-7.34 (m, 1H), 7.04-7.01 (m, 1H), 6.95 (t, J=9.6 Hz, 1H), 2.47 (s, 3H). LCMS: 271.1 (M+1)+

후처리

  1. temperatureThe mixture was then refluxed for 2 h
  2. temperatureThe combined mixture was refluxed for 12 h
  3. concentrationAfter concentration under vacuum, water (20 mL) and HCl (10 mL, aq. 1N)
  4. additionwere added
  5. customThe suspended solids were collected
  6. washwashed with water (50 mL×3) and EtOH (50 mL×3)
  7. customdried

출처 및 근거

ORD 기록
ord-7b8f3775189841e191d8dad421db2478
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115114B2

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