Cesium carbonate → 4-(2-Fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester

HRID 15931

反応式

HRID 15931 の反応式
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH2:9].C1(P(C2C=CC=CC=2)C2(P(C3C=CC=CC=3)C3C=CC=CC=3)CC=C3C(C=CC=C3)=C2C2C3C(=CC=CC=3)C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:62]([O:64][C:65]([C:67]1[C:72](Cl)=[C:71]([CH3:74])[C:70](=[O:75])[N:69]([CH3:76])[C:68]=1[CH3:77])=[O:66])[CH3:63]>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:62]([O:64][C:65]([C:67]1[C:72]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[F:1])=[C:71]([CH3:74])[C:70](=[O:75])[N:69]([CH3:76])[C:68]=1[CH3:77])=[O:66])[CH3:63]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 679842-Fluoro-4-methylanilineHCID 666739724-Chloro-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl esterHCID 86595863(+/-)-2,2-Bis(diphenylphosphino)-1,1-binaphthyl

生成物 1

HCID 666746314-(2-Fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester収率 71%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

2-Fluoro-4-methylphenylamine (0.259 g, 2.07 mmol), palladium (II) acetate (0.046 g, 0.205 mmol), rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (0.192 g, 0.308 mmol), and cesium carbonate (1.00 g, 3.08 mmol) were added to a solution of 4-chloro-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester (0.50 g, 2.05 mmol) in toluene (7 mL) in a sealed vial. After stirring 10 minutes, the mixture was heated to 80° C. After 24 hours, the reaction mixture was cooled to room temperature and diluted with EtOAc. The resulting precipitate was filtered and washed with EtOAc. The filtrate was diluted with EtOAc and washed with water. The aqueous layer was reextracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography (20:1 methylene chloride/MeOH) gave 0.048 g (71%) desired product.

後処理

  1. waitAfter 24 hours
  2. temperaturethe reaction mixture was cooled to room temperature
  3. filtrationThe resulting precipitate was filtered
  4. washwashed with EtOAc
  5. additionThe filtrate was diluted with EtOAc
  6. washwashed with water
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by flash column chromatography (20:1 methylene chloride/MeOH)

出典と根拠

ORDレコード
ord-e69eff02af2941c1807202bb1f188821
出典データセット
uspto-grants-2010_06
特許番号
US07732616B2

関連ノート

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