Cesium fluoride → 6-(4-Fluorophenyl)pyridine-3-carboxylic acid methyl ester

HRID 2053700노트

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HRID 2053700 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8](Br)=[CH:9][CH:10]=1)=[O:4].[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.[F-].[Cs+]>CN(C=O)C.O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=2)=[CH:9][CH:10]=1)=[O:4]

참가 물질

8

반응물 3

HCID 25953Cesium fluorideHCID 2856454-Fluorophenylboronic acidHCID 13349623Methyl 6-bromopyridine-3-carboxylate

생성물 1

HCID 110317126-(4-Fluorophenyl)pyridine-3-carboxylic acid methyl ester

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

Combine 6-bromopyridine-3-carboxylic acid methyl ester (1.03 g, 4.78 mmol), 4-fluorophenylboronic acid (1.88 g, 13.41 mmol), and cesium fluoride (2.55 g, 16.78 mmol) in DMF (25 mL) and water (4 mL) with stirring. Place the hetereogeneous reaction mixture, open to the air, in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (150 mg, 0.67 mmol) in one portion. After 17 hours, cool the reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over MgSO4, filter and evaporate. Purification by flash column chromatography yields 6-(4-fluorophenyl)pyridine-3-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1M NaOH. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCL and collect the white precipitate by filtration. Drying under vacuum yields 385 mg (37%) of the title compound. MS (m/e): 218.1 (MH+)

후처리

  1. temperatureAfter 5 minutes of heating
  2. temperaturecool
  3. customthe reaction to room temperature
  4. filtrationfilter through a short plug of celite with additional ethyl acetate
  5. washWash the organics with water
  6. dry with materialdry over MgSO4
  7. filtrationfilter
  8. customevaporate
  9. customPurification by flash column chromatography

출처 및 근거

ORD 기록
ord-1772c3ebd77f4e63958a6dd7b03d70b9
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07326731B2

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