海萝胶 → 3-(5-Fluoro-pyridin-2-yl)-isoxazole-4-carboxylic acid ethyl ester

HRID 83463

反应方程式

HRID 83463 反应方程式
ClN1C(=O)CCC1=O.[F:9][C:10]1[CH:11]=[CH:12][C:13]([CH:16]=[N:17][OH:18])=[N:14][CH:15]=1.CN([CH:22]=[CH:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])C.C(N(CC)CC)C.Cl>CN(C=O)C.C(Cl)(Cl)Cl>[CH2:27]([O:26][C:24]([C:23]1[C:16]([C:13]2[CH:12]=[CH:11][C:10]([F:9])=[CH:15][N:14]=2)=[N:17][O:18][CH:22]=1)=[O:25])[CH3:28]

参与物

8

反应物 5

HCID 313海萝胶HCID 8471三乙胺HCID 31398N-氯代丁二酰亚胺HCID 1210153-(N,N-二甲基氨基)丙烯酸乙酯HCID 1363872515-Fluoro-pyridine-2-carbaldehyde oxime

产物 1

HCID 666436143-(5-Fluoro-pyridin-2-yl)-isoxazole-4-carboxylic acid ethyl ester收率 72%

试剂、催化剂与溶剂 2

HCID 6212三氯甲烷溶剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
60 °C

实验过程

To a solution of N-chlorosuccinimide (17.34 g, 130 mmol) in DMF (128 mL) was added 5-fluoro-pyridine-2-carbaldehyde oxime (18.2 g, 130 mmol) portionwise over 2 h at room temperature and as the reaction warmed up to 60° C. the mixture was cooled back to room temperature with an ice-water bath and the resulting mixture was then stirred for 64 h at room temperature. To this solution was then added ethyl 3-(N,N-dimethylamino)acrylate (18.6 g, 130 mmol) and triethylamine (36.2 mL, 260 mmol) in chloroform (64 mL) and the resulting mixture was then stirred for 1 h at room temperature and poured onto a mixture of ice water and HCl (4 N, 1 L) and extracted with ethylacetate. The organic extract was then washed with water, saturated aqueous sodium hydrogen carbonate solution, brine, dried with sodium sulfate, filtered and evaporated. Purification by chromatography (SiO2, heptane:ethylacetate=100:0 to 1:1) afforded the title product (21.96 g, 72%) which was obtained as a yellow solid. MS: m/e=237.1 [M+H]+.

后处理

  1. temperaturewas cooled back to room temperature with an ice-water bath
  2. extractionextracted with ethylacetate
  3. extractionThe organic extract
  4. washwas then washed with water, saturated aqueous sodium hydrogen carbonate solution, brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by chromatography (SiO2, heptane:ethylacetate=100:0 to 1:1)

来源与证据

ORD记录
ord-2681dd3e508647f09aa662550c4cca41
来源数据集
uspto-grants-2014_09
专利号
US08846719B2

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