Ethyl Acetate → 5-Bromo-2-(6-chloropyridin-3-yloxy)-4-fluorobenzoic acid

HRID 335895노트

반응식

HRID 335895 반응식
[Br:1][C:2]1[C:3]([F:12])=[CH:4][C:5](I)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[Cl:13][C:14]1[N:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>O.CCOCC>[Br:1][C:2]1[C:3]([F:12])=[CH:4][C:5]([O:20][C:17]2[CH:18]=[N:19][C:14]([Cl:13])=[CH:15][CH:16]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]

참가 물질

7

반응물 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 8198212-Chloro-5-hydroxypyridineHCID 673830505-Bromo-4-fluoro-2-iodobenzoic acid

생성물 1

HCID 866584825-Bromo-2-(6-chloropyridin-3-yloxy)-4-fluorobenzoic acid

시약·촉매·용매 2

HCID 962Water용매HCID 3283Diethyl Ether용매

반응 조건

온도
115 °C

실험 절차

A flask was charged with 5-bromo-4-fluoro-2-iodobenzoic acid (4.00 g, 11.60 mmol), 6-chloropyridin-3-ol (1.803 g, 13.92 mmol), and cesium carbonate (7.56 g, 23.19 mmol). The flask was evacuated and flushed with nitrogen twice before copper (I) trifluoromethanesulfonate toluene complex (0.156 g, 0.302 mmol) was added. Toluene (58.0 mL) (degassed 10 minutes by bubbling nitrogen through the solution prior to use) and ethyl acetate (0.084 mL, 0.858 mmol) were added and the mixture was heated at 115° C. After 2 hours, the reaction was allowed to cool to RT and the mixture was diluted with water (50 mL) and stirred vigorously for 15 minutes. After diluting with ether (200 mL), the layers were separated and the organic layer was extracted with 10% sodium carbonate. The pH of the combined aqueous layers was adjusted to pH ˜2 and extracted with ethyl acetate. The combined organic layers were washed with saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated to afford 5-bromo-2-(6-chloropyridin-3-yloxy)-4-fluorobenzoic acid as a solid. MS m/z=347.9 [M+H].

후처리

  1. customThe flask was evacuated
  2. customflushed with nitrogen twice before copper (I) trifluoromethanesulfonate toluene complex (0.156 g, 0.302 mmol)
  3. additionwas added
  4. customToluene (58.0 mL) (degassed 10 minutes
  5. customby bubbling nitrogen through the solution
  6. additionwere added
  7. temperatureto cool to RT
  8. customthe layers were separated
  9. extractionthe organic layer was extracted with 10% sodium carbonate
  10. extractionextracted with ethyl acetate
  11. washThe combined organic layers were washed with saturated sodium chloride
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

출처 및 근거

ORD 기록
ord-59e6e3642fd54fb7b213c648158b221a
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883782B2

반응 노트

불러오는 중…