三乙胺 → (Z)-Ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate

HRID 1497690

反应方程式

HRID 1497690 反应方程式
[CH3:1][N:2]([CH3:10])/[CH:3]=[CH:4]/[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(N(CC)CC)C.[F:18][C:19]1[C:20]([C:25](Cl)=[O:26])=[N:21][CH:22]=[CH:23][CH:24]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][N:2]([CH3:10])/[CH:3]=[C:4](/[C:25](=[O:26])[C:20]1[C:19]([F:18])=[CH:24][CH:23]=[CH:22][N:21]=1)\[C:5]([O:7][CH2:8][CH3:9])=[O:6]

参与物

6

反应物 3

HCID 8471三乙胺HCID 5369162N,N-二甲氨基丙烯酸乙酯HCID 861023073-Fluoropyridine-2-carbonyl chloride

产物 1

HCID 86725445(Z)-Ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate收率 16.6%

试剂、催化剂与溶剂 2

HCID 1140甲苯溶剂2 次HCID 8857乙酸乙酯溶剂

反应条件

温度
83 °C

实验过程

To a light yellow solution of (E)-ethyl 3-(dimethylamino)acrylate (5.15 g, 36.0 mmol) in toluene (50 mL) was added triethylamine (3.64 g, 5.02 mL, 36.0 mmol) at room temperature. To this, a dark brown suspension of 3-fluoropicolinoyl chloride (30) (4.79 g, 30 mmol) in toluene (50 mL, heated to dissolve, but not dissolved completely) was added in one portion using a funnel. Then, the resulting dark brown solution was heated to 83° C. and stirred for 1.5 h at this temperature. During this period, it turned to a dark brown solution and TLC analysis indicated the presence of a new spot. Then, the heating was stopped and the dark brown mixture was diluted with ethyl acetate (200 mL) and the brown solution was washed with water, brine solution, and dried over anhydrous MgSO4. Filtration and concentration gave the crude brown mixture which was purified using ISCO (120 g) column chromatography, eluting with ethyl acetate in hexanes (0 to 100%) and then 5 to 20% methanol in dichloromethane. The desired fractions were combined and the solvent was removed under vacuum to obtain the (Z)-ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate (31) (1.33 g, 15% yield) as a dark brown paste.

后处理

  1. temperatureheated
  2. dissolutionto dissolve
  3. dissolutionnot dissolved completely)
  4. additionwas added in one portion
  5. waitDuring this period
  6. washthe brown solution was washed with water, brine solution
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationFiltration and concentration
  9. customgave the crude brown mixture which
  10. customwas purified
  11. washeluting with ethyl acetate in hexanes (0 to 100%)
  12. customthe solvent was removed under vacuum

来源与证据

ORD记录
ord-cf5c752ae14e40ab8d18cc68d78a5194
来源数据集
uspto-grants-2015_12
专利号
US09199987B2

关联笔记

加载中…