Hydrochloric Acid → 4-((5-Chloro-6-isopropoxypyridin-3-yl)methoxy)-2,5-difluorobenzoic acid

HRID 512041ノート

反応式

HRID 512041 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][O:10][C:11]2[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:21])[CH:12]=2)[CH:5]=[N:6][C:7]=1Cl.[H-].[Na+].[CH:24]([OH:27])([CH3:26])[CH3:25].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][O:10][C:11]2[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:21])[CH:12]=2)[CH:5]=[N:6][C:7]=1[O:27][CH:24]([CH3:26])[CH3:25]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 24758Sodium hydrideHCID 866825694-((5,6-Dichloropyridin-3-yl)methoxy)-2,5-difluorobenzoic acid

生成物 1

HCID 666679654-((5-Chloro-6-isopropoxypyridin-3-yl)methoxy)-2,5-difluorobenzoic acid収率 46%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

To a solution of 4-((5,6-dichloropyridin-3-yl)methoxy)-2,5-difluorobenzoic acid (Preparation 14, 210 mg, 0.67 mmol) in THF (5 mL) was added an oil dispersion of NaH (60%, 157 mg, 3.93 mmol) followed by iso-propanol (5 mL) and the reaction mixture was warmed to 80° C. and stirred for 18 hours under a nitrogen atmosphere. Aqueous hydrogen chloride solution (1 M, 20 mL) was added and the mixture extracted with EtOAc (3×30 mL). The combined organics were dried over magnesium sulfate and the solvent was removed in vacuo. The resulting crude was purified by reverse phase chromatography eluting with H2O/MeCN/HCOOH (95/5/0.1 to 5/95/0.1, Biotage™ 40 g C18-silica gel) to yield the title compound (105 mg, 46%).

後処理

  1. extractionthe mixture extracted with EtOAc (3×30 mL)
  2. dry with materialThe combined organics were dried over magnesium sulfate
  3. customthe solvent was removed in vacuo
  4. customThe resulting crude was purified by reverse phase chromatography
  5. washeluting with H2O/MeCN/HCOOH (95/5/0.1 to 5/95/0.1, Biotage™ 40 g C18-silica gel)

出典と根拠

ORDレコード
ord-db8f5c53aa5a448294cec6fe5b1f7ed0
出典データセット
uspto-grants-2015_08
特許番号
US09102621B2

反応ノート

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