氟化铯 → 1,1-Dimethylethyl [2-[1-(ethyloxy)ethenyl]-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate

HRID 15130

反应方程式

HRID 15130 反应方程式
Cl[C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][C:5]([F:16])=[C:4]([O:17][CH3:18])[N:3]=1.[F-].[Cs+].C([Sn](CCCC)(CCCC)[C:26]([O:28][CH2:29][CH3:30])=[CH2:27])CCC.[F-].[K+]>O1CCOCC1.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[CH2:29]([O:28][C:26]([C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][C:5]([F:16])=[C:4]([O:17][CH3:18])[N:3]=1)=[CH2:27])[CH3:30]

参与物

7

反应物 4

HCID 25953氟化铯HCID 522689氟化钾HCID 619414三丁基(1-乙氧基乙烯)锡HCID 71463986(2-氯-5-氟-6-甲氧基吡啶-3-基)氨基甲酸叔丁酯

产物 1

HCID 866141461,1-Dimethylethyl [2-[1-(ethyloxy)ethenyl]-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate

试剂、催化剂与溶剂 2

HCID 2734558二(三叔丁基膦)钯催化剂HCID 312751,4-二氧六环溶剂

反应条件

温度
100 °C

实验过程

A degassed solution of 1,1-dimethylethyl [2-chloro-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate (20 g, 72.2 mmol) in 1,4-dioxane (200 ml) was treated with bis(tri-tert-butylphosphine) palladium(0) (1.05 g), caesium fluoride (21.93 g) and tributyl[1-(ethyloxy)ethenyl]stannane (26.9 ml) then heated to 100° C. overnight. The cooled mixture was treated with 10% aqueous potassium fluoride solution. After 0.5 hour stirring, the mixture was filtered through Kieselguhr, washing with 1,4-dioxane. Ethyl acetate and water were added to the filtrate. The phases were separated and the aqueous phase extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was rapidly chromatographed eluting with 25-50% dichloromethane in hexane affording the product as a light brown oil (22.2 g, 99%).

后处理

  1. filtrationthe mixture was filtered through Kieselguhr
  2. washwashing with 1,4-dioxane
  3. additionEthyl acetate and water were added to the filtrate
  4. customThe phases were separated
  5. extractionthe aqueous phase extracted twice with ethyl acetate
  6. dry with materialThe combined organic extracts were dried over magnesium sulphate
  7. customevaporated
  8. customThe residue was rapidly chromatographed
  9. washeluting with 25-50% dichloromethane in hexane affording the product as a light brown oil (22.2 g, 99%)

来源与证据

ORD记录
ord-7f2d49d4ac4a426ea06dc7242d782435
来源数据集
uspto-grants-2010_06
专利号
US07732460B2

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