Reaction #1135869

Reaction equation

sodium hydride

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

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

sodium iodide

ethyl 2-hydroxyacetate

→

2-(imidazo[1,2-a]pyridin-2-ylmethoxy)acetic acid

Yield 69.1%

Solvents

tetrahydrofurane

tetrahydrofurane

tetrahydrofurane

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at r.t. for 3 h
2. 2
   workup.STIRRINGThe mixture was stirred 15 min at 0° C.
3. 3
   workup.STIRRINGThe mixture was stirred at r.t. for 24 h
4. 4
   Filtrationbefore being filtered on silica (eluent: tetrahydrofurane 100%)
5. 5
   ConcentrationThe filtrate was concentrated in vacuo
6. 6
   Otherdirectly purified by flash chromatography on a silica gel cartridge (eluent
7. 7
   Washand then washing the cartridge with 100% methanol)

Procedure

4.24 g (25.4 mmol) of 2-(chloromethyl)imidazo[1,2-a]pyridine were dissolved in 150 ml of tetrahydrofurane with magnetic stirring and then 4.2 g (28 mmol) of sodium iodide were added. The mixture was stirred at r.t. for 3 h. In another flask, 9.84 ml (101.8 mmol) of ethyl 2-hydroxyacetate were solubilized in 100 ml of tetrahydrofurane with magnetic stirring, and then the mixture was cooled to 0° C. and 4.072 g (101.8 mmol) of sodium hydride were added portionwise. The mixture was stirred 15 min at 0° C. and then the freshly prepared solution of 2-(iodomethyl)imidazo[1,2-a]pyridine in tetrahydrofurane was added drop wise within 15 min. The mixture was stirred at r.t. for 24 h before being filtered on silica (eluent: tetrahydrofurane 100%). The filtrate was concentrated in vacuo and directly purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol gradient, from 100% to 70% of dichloromethane, v/v; and then washing the cartridge with 100% methanol). 3.62 g (yield=69%) of 2-(imidazo[1,2-a]pyridin-2-ylmethoxy)acetic acid were obtained as a beige solid. LC-MS: m/z=207 (MH+); UV purity at 254 nm=98%.

Source