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

HRID 518359

反応式

HRID 518359 の反応式
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

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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)+

後処理

  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

出典と根拠

ORDレコード
ord-7b8f3775189841e191d8dad421db2478
出典データセット
uspto-grants-2015_08
特許番号
US09115114B2

関連ノート

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