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

HRID 518359

Reaktionsgleichung

Reaktionsgleichung von HRID 518359
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

Komponenten

8

Edukt 5

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

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)+

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7b8f3775189841e191d8dad421db2478
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115114B2

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