Reaction #1135868

Reaction equation

1,3-dichloroacetone

2-aminopyridine

→

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

Yield 55.0%

Solvents

DME

Conditions

Workup

1. 1
   OtherThe solid formed
2. 2
   Otherwas isolated by filtration
3. 3
   Washwashed with 30 ml of diisopropyl ether
4. 4
   workup.STIRRINGthe mixture was stirred
5. 5
   Temperaturewith reflux for 2 h
6. 6
   ConcentrationThe mixture was concentrated in vacuo
7. 7
   workup.ADDITIONby adding a saturated NaHCO3 aqueous solution
8. 8
   ExtractionThe aqueous phase was extracted with 3×100 ml of dichloromethane
9. 9
   WashThe combined organic phases were washed with 200 ml of a saturated NaCl aqueous solution
10. 10
    Otherdried on Na2SO4 which
11. 11
    Otherwas then removed by filtration
12. 12
    ConcentrationThe obtained filtrate was concentrated in vacuo
13. 13
    OtherThe 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)

Procedure

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)

Source