Lithium Hydroxide → 3-{[4-(4,5-Difluorobenzofuran-7-yl)-2-fluoro-phenoxy]methyl}benzoic acid

HRID 928675ノート

反応式

HRID 928675 の反応式
[F:1][C:2]1C=[C:6](O)[CH:5]=[CH:4][C:3]=1B(O)O.Br[C:13]1[C:21]2[O:20][CH:19]=[CH:18][C:17]=2[C:16]([F:22])=[C:15]([F:23])[CH:14]=1.[C:24](=[O:27])([O-])[O-:25].[Na+].[Na+].BrC[C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=1)[C:35]([O:37][CH3:38])=O.C(=O)([O-])[O-].[K+].[K+].[OH-].[Li+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1.O.CO.CN(C=O)C.O1CCOCC1>[F:22][C:16]1[C:17]2[CH:18]=[CH:19][O:20][C:21]=2[C:13]([C:4]2[CH:5]=[CH:6][C:38]([O:37][CH2:35][C:34]3[CH:39]=[C:40]([CH:41]=[CH:32][CH:33]=3)[C:24]([OH:25])=[O:27])=[C:2]([F:1])[CH:3]=2)=[CH:14][C:15]=1[F:23]

参加物

14

反応物 6

HCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 517981Methyl 3-(bromomethyl)benzoateHCID 221448747-Bromo-4,5-difluorobenzofuranHCID 567376732-Fluoro-4-hydroxyphenylboronic acid

生成物 1

HCID 903843853-{[4-(4,5-Difluorobenzofuran-7-yl)-2-fluoro-phenoxy]methyl}benzoic acid収率 24%

試薬・触媒・溶媒 7

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 887Methanol溶媒HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

1,4-Dioxane (12 mL) and water (4 mL) were added to 2-fluoro-4-hydroxyphenylboronic acid (475 mg, 3.0 mmol), 7-bromo-4,5-difluoro-1-benzofuran (590 mg, 2.53 mmol), sodium carbonate (540 mg, 5.1 mmol), and Pd(dppf)Cl2 (catalytic amount), and stirred at 100° C. for 2 hours. The reaction solution was concentrated under reduced pressure. To the residue, ethyl acetate and 1 N hydrochloric acid were added and stirred. After that, the insoluble material was filtered off, and extraction was performed with ethyl acetate. The organic phase was washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. Then, to the resulting residue, methyl 3-(bromomethyl)benzoate (595 mg, 2.6 mmol), potassium carbonate (414 mg, 3.0 mmol), and DMF (4 mL) were added, and stirred overnight. After diluted with ethyl acetate, the resultant was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. To the resulting residue, methanol (5 mL), water (2 mL), THF (5 mL), and lithium hydroxide (210 mg, 5.0 mmol) were added, and stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and extraction was performed with ethyl acetate. The organic phase was washed with saturated brine, and then dried over anhydrous magnesium sulfate. After the solvent was distilled away under reduced pressure, the resulting solid was collected by filtration to thus obtain the title compound.

後処理

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionTo the residue, ethyl acetate and 1 N hydrochloric acid were added
  3. stirringstirred
  4. filtrationAfter that, the insoluble material was filtered off
  5. extractionextraction
  6. washThe organic phase was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled away under reduced pressure
  9. stirringstirred overnight
  10. washthe resultant was washed with water and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. distillationThe solvent was distilled away under reduced pressure
  13. stirringstirred at room temperature overnight
  14. concentrationThe reaction solution was concentrated under reduced pressure, and extraction
  15. washThe organic phase was washed with saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. distillationAfter the solvent was distilled away under reduced pressure
  18. filtrationthe resulting solid was collected by filtration

出典と根拠

ORDレコード
ord-f277e21dedb7467cb1c83838cfee3267
出典データセット
uspto-grants-2016_03
特許番号
US09290487B2

反応ノート

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