Citric Acid → HCID 86641942、化合物

HRID 384118ノート

反応式

HRID 384118 の反応式
CO[C:3]([C:5]1[C:10](F)=[CH:9][CH:8]=[C:7]([Cl:12])[N:6]=1)=[O:4].[C:13]1([OH:19])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.O>[Cl:12][C:7]1[N:6]=[C:5]([CH2:3][OH:4])[C:10]([O:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1

参加物

10

反応物 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 996PhenolHCID 11430Potassium CarbonateHCID 46311240HCID 46311240、化合物

生成物 1

HCID 86641942HCID 86641942、化合物

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒HCID 21225700Diisobutylaluminumhydride溶媒

反応条件

温度
100 °C

実験手順

To a solution of 6-chloro-3-fluoropyridin-2-carboxylic acid methyl ester (245 mg) in dimethylformamide (3 ml), 200 mg of phenol and 393 mg of potassium carbonate were added, and the reaction solution was stirred at 100° C. for 1.5 hours. The reaction solution was cooled, then 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a brown oil. To a solution of the crude product in toluene (5 ml), 9.9 ml of diisobutylaluminum hydride (1.0M hexane solution) was added at −78° C., and the reaction solution was stirred for 2 hours while increasing the temperature of the reaction solution to room temperature. To the reaction solution were added water and 10% aqueous citric acid sequentially, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50)) to afford the title compound as a pale yellow oil.

後処理

  1. temperatureThe reaction solution was cooled
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with a saturated saline solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customto afford a crude product as a brown oil
  7. stirringthe reaction solution was stirred for 2 hours
  8. temperaturewhile increasing the temperature of the reaction solution to room temperature
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe combined organic layers were washed with a saturated saline solution
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off under reduced pressure
  13. customthe residue obtained
  14. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50))

出典と根拠

ORDレコード
ord-14d89ee2882e4809af2adf771bbc64fd
出典データセット
uspto-grants-2013_02
特許番号
US08367708B2

反応ノート

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