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

HRID 1837453노트

반응식

HRID 1837453 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6342Acetonitrile용매HCID 8471Triethylamine용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-009b1d8a67404275b1c35f58e9a27735
출처 데이터셋
uspto-grants-2004_08
특허 번호
US06784137B2

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