Cesium fluoride → Methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate

HRID 1837453ノート

反応式

HRID 1837453 の反応式
[CH3:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[CH3:8].[F-].[Cs+].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:44][C:45]1[CH:50]=[C:49](Cl)[N:48]=[C:47]([C:52]([O:54][CH3:55])=[O:53])[C:46]=1[Cl:56]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(N(CC)CC)C>[NH2:44][C:45]1[CH:50]=[C:49]([C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([CH3:1])[CH:3]=2)[N:48]=[C:47]([C:52]([O:54][CH3:55])=[O:53])[C:46]=1[Cl:56]

参加物

9

反応物 4

HCID 25953Cesium fluorideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 27343483,4-Dimethylphenylboronic acidHCID 22677331Methyl 4-amino-3,6-dichloropyridine-2-carboxylate

生成物 1

HCID 22677522Methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate収率 50%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8471Triethylamine溶媒

実験手順

A solution of 3,4-dimethylphenylboronic acid (2.1 g, 14.0 mmol), cesium fluoride (6.3 g, 41.5 mmol), 1,4-bis(diphenylphosphino)butane (0.5 g, 1.2 mmol), methyl 4-amino-3,6-dichloropyridine-2-carboxylate (2.5 g, 10.0 mmol) and triethylamine (5 mL) in acetonitrile (100 mL) was sparged for thirty minutes with nitrogen. Palladium acetate (0.3 g, 1.2 mmol) was added and the reaction mixture heated under reflux for three hours. After cooling water (200 mL) was added and the mixture extracted with ethyl acetate (2×100 mL). The organic layer was washed with brine (100 mL), dried (NaSO4), and concentrated. The residue was purified by column chromatography (33 percent ethyl acetate in hexane) to give methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate (1.4 g, 5.0 mmol), mp 154-156° C.

後処理

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux for three hours
  3. additionwas added
  4. extractionthe mixture extracted with ethyl acetate (2×100 mL)
  5. washThe organic layer was washed with brine (100 mL)
  6. dry with materialdried (NaSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (33 percent ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-009b1d8a67404275b1c35f58e9a27735
出典データセット
uspto-grants-2004_08
特許番号
US06784137B2

反応ノート

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