反应 #1135868

反应方程式

1,3-dichloroacetone

2-aminopyridine

→

2-(chloromethyl)imidazo[1,2-a]pyridine

收率 55.0%

溶剂

DME

反应条件

后处理

1. 1
   其他The solid formed
2. 2
   其他was isolated by filtration
3. 3
   洗涤washed with 30 ml of diisopropyl ether
4. 4
   workup.STIRRINGthe mixture was stirred
5. 5
   温度with reflux for 2 h
6. 6
   浓缩The mixture was concentrated in vacuo
7. 7
   workup.ADDITIONby adding a saturated NaHCO3 aqueous solution
8. 8
   萃取The aqueous phase was extracted with 3×100 ml of dichloromethane
9. 9
   洗涤The combined organic phases were washed with 200 ml of a saturated NaCl aqueous solution
10. 10
    其他dried on Na2SO4 which
11. 11
    其他was then removed by filtration
12. 12
    浓缩The obtained filtrate was concentrated in vacuo
13. 13
    其他The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, from 50% to 40% of heptane, v/v)

实验过程

7.09 g (54.1 mmol) of 1,3-dichloroacetone were solubilised in 13 ml of DME, to this solution were added with magnetic stirring, 5 g (52.1 mmol) of 2-aminopyridine. The mixture was stirred at r.t. for 16 h. The solid formed was isolated by filtration and washed with 30 ml of diisopropyl ether. This yellow solid was suspended in 125 ml of absolute ethanol and the mixture was stirred with reflux for 2 h. The mixture was concentrated in vacuo and then the obtained residue was taken up in 150 ml of a mixture consisting of water and ice. The pH of the aqueous phase was basified up to pH 8-9 by adding a saturated NaHCO3 aqueous solution. The aqueous phase was extracted with 3×100 ml of dichloromethane. The combined organic phases were washed with 200 ml of a saturated NaCl aqueous solution, dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, from 50% to 40% of heptane, v/v). 4.77 g (yield=55%) of 2-(chloromethyl)imidazo[1,2-a]pyridine were obtained as a white solid. LC-MS: m/z=167 (MH+); UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.52 (d, J=6.8 Hz, 1H), 7.99 (s, 1H), 7.51 (d, J=9.1 Hz, 1H), 7.32-7.16 (m, 1H), 6.89 (t, J=6.8 Hz, 1H), 4.84 (s, 2H)

来源