2,4-Dichloroaniline → 5-Cyclopropyl-6-(2,4-dichloro-phenylamino)-pyridine-2-carboxylic acid methyl ester

HRID 927337

反応式

HRID 927337 の反応式
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:26][O:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([CH:36]2[CH2:38][CH2:37]2)=[C:32](Cl)[N:31]=1)=[O:29].[Cl:40][C:41]1[CH:47]=[C:46]([Cl:48])[CH:45]=[CH:44][C:42]=1[NH2:43].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:26][O:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([CH:36]2[CH2:38][CH2:37]2)=[C:32]([NH:43][C:42]2[CH:44]=[CH:45][C:46]([Cl:48])=[CH:47][C:41]=2[Cl:40])[N:31]=1)=[O:29]

参加物

7

反応物 4

HCID 111232,4-DichloroanilineHCID 11430Potassium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 866747356-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid methyl ester

生成物 1

HCID 710873965-Cyclopropyl-6-(2,4-dichloro-phenylamino)-pyridine-2-carboxylic acid methyl ester収率 39%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒2 回

実験手順

A solution of palladium(II)acetate (4.24 mg, 18.9 μmol) and 2-(dicyclohexylphosphino) biphenyl (13.2 mg, 37.8 μmol) in dioxane (1.9 ml) under an argon atmosphere was stirred for 10 min at ambient temperature and subsequently added to a suspension of 6-chloro-5-cyclopropyl-pyridine-2-carboxylic acid methyl ester (100 mg, 472 μmol), 2,4-dichloroaniline (76.6 mg, 472 μmol) and potassium carbonate (1.31 g, 9.45 mmol) in dioxane (3.24 ml) under an argon atmosphere. The yellow suspension was heated to reflux and stirred for 20 h. The reaction mixture was poured into 20 mL ice/brine and extracted with i-PrOAc (2×50 mL). The combined organic layers were washed with ice/brine (1×50 mL), dried over sodium sulfate and concentrated in vacuo to give a brown oil. The crude product was purified by flash chromatography (silica gel, 4 g, 0% to 10% heptane/iPrOAc) to give the title compound (62 mg, 39%) as light brown liquid, MS (EI): m/e=337.2 [M+H]+.

後処理

  1. temperatureThe yellow suspension was heated
  2. temperatureto reflux
  3. extractionextracted with i-PrOAc (2×50 mL)
  4. washThe combined organic layers were washed with ice/brine (1×50 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. customThe crude product was purified by flash chromatography (silica gel, 4 g, 0% to 10% heptane/iPrOAc)

出典と根拠

ORDレコード
ord-8af34e6b5ff84bb28b0e056ce7af62f8
出典データセット
uspto-grants-2016_03
特許番号
US09290451B2

関連ノート

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