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

HRID 512041노트

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HRID 512041 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-db8f5c53aa5a448294cec6fe5b1f7ed0
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102621B2

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