Cesium fluoride → 4-Acetylamino-3-chloro-6-(2-fluoro-3-methoxy-4-trifluoromethylphenyl)pyridine-2-carboxylic acid methyl ester

HRID 1782617

반응식

HRID 1782617 반응식
[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[C:9]([NH:12][C:13](=[O:15])[CH3:14])[CH:8]=[C:7](Cl)[N:6]=1)=[O:4].[F:17][C:18]1[C:23]([O:24][CH3:25])=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=[CH:20][C:19]=1[Sn](C)(C)C.[F-].[Cs+].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[C:9]([NH:12][C:13](=[O:15])[CH3:14])[CH:8]=[C:7]([C:19]2[CH:20]=[CH:21][C:22]([C:26]([F:28])([F:29])[F:27])=[C:23]([O:24][CH3:25])[C:18]=2[F:17])[N:6]=1)=[O:4]

참가 물질

7

반응물 4

HCID 25953Cesium fluorideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 22677481Methyl 4-acetamido-3,6-dichloropyridine-2-carboxylateHCID 68810358(2-Fluoro-3-methoxy-4-trifluoromethylphenyl)trimethyl stannane

생성물 1

HCID 688110344-Acetylamino-3-chloro-6-(2-fluoro-3-methoxy-4-trifluoromethylphenyl)pyridine-2-carboxylic acid methyl ester수율 10%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6342Acetonitrile용매

실험 절차

In an oven dried, nitrogen flushed 100 mL 3 neck flask equipped with a condenser and a magnetic stirbar was dissolved methyl-4-acetamido-3,6-dichloropyridine-2-carboxylate (1.2 g, 4.6 mmol) and (2-fluoro-3-methoxy-4-trifluoromethylphenyl)trimethyl stannane (1.7 g, 4.6 mmol) in acetonitrile (15 mL) and the resulting solution was de-aerated with a purge of nitrogen for 15 minutes. Cesium fluoride (2.1 g, 13.9 mmol), 1,4-bis(diphenylphosphino)butane (0.2 g, 0.46 mmol) and palladium acetate (0.1 g, 0.46 mmol) were added and the head space of the reaction was purged with nitrogen as the reaction was heated to reflux with stirring. The reaction was then stirred under an open nitrogen atmosphere for 5 hours by which time TLC (hexane:ethyl acetate/1:2) indicated complete consumption of starting material. The cooled reaction was filtered through celite with ethyl acetate and the filtrate concentrated and purified by flash silica gel chromatography (hexanes:ethyl acetate/2:1) to give 4-acetylamino-3-chloro-6-(2-fluoro-3-methoxy-4-trifluoromethylphenyl)pyridine-2-carboxylic acid methyl ester (0.19 g, 0.46 mmol) as an oil: 1H NMR (CDCl3): δ 9.03 (d, 1H), 8.02 (bs, 1H), 7.68 (bt, 1H), 7.42 (bd, 1H), 4.03 (d, 3H), 4.01 (s, 3H), 2.33 (s, 3H).

후처리

  1. customIn an oven dried
  2. customnitrogen flushed 100 mL 3 neck flask
  3. customequipped with a condenser
  4. customa purge of nitrogen for 15 minutes
  5. customthe head space of the reaction was purged with nitrogen as the reaction
  6. temperaturewas heated
  7. temperatureto reflux
  8. stirringThe reaction was then stirred under an open nitrogen atmosphere for 5 hours by which time TLC (hexane:ethyl acetate/1:2)
  9. customconsumption of starting material
  10. customThe cooled reaction
  11. filtrationwas filtered through celite with ethyl acetate
  12. concentrationthe filtrate concentrated
  13. custompurified by flash silica gel chromatography (hexanes:ethyl acetate/2:1)

출처 및 근거

ORD 기록
ord-ef88bfceac19452d82b5de6467be35e3
출처 데이터셋
uspto-grants-2009_03
특허 번호
US07498468B2

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