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

HRID 2053700ノート

反応式

HRID 2053700 の反応式
[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]

参加物

8

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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+)

後処理

  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

出典と根拠

ORDレコード
ord-1772c3ebd77f4e63958a6dd7b03d70b9
出典データセット
uspto-grants-2008_02
特許番号
US07326731B2

反応ノート

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