Acetic Acid → Ethyl 3-(hydroxymethyl)imidazo[1,2-a]pyridine-8-carboxylate

A mixture of ethyl imidazo[1,2-a]pyridine-8-carboxylate (1 g, 5.26 mmol), sodium acetate (1.725 g, 21.03 mmol), formaldehyde (36.5% wt. in water, 2.5 mL, 33.1 mmol) and acetic acid (1.145 mL, 20 mmol) was stirred at room temperature for 3 hours. The reaction mixture was then heated at reflux for a further 4 hours and then cooled and diluted with water (50 mL). The pH was adjusted to 8 with saturated aqueous sodium hydrogen carbonate solution (ca. 10 mL) and the solution was extracted successively with ethyl acetate (3×50 mL) and 3:1 chloroform:isopropanol (100 mL). The organic extracts were combined, washed successively with saturated sodium bicarbonate (50 mL) and brine (50 mL) and dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was dissolved in dichloromethane and purified on a silica cartridge (100 g) using a 0-30% methanol (+1% Et3N)-DCM gradient over 60 mins. The product containing fractions were combined and evaporated in vacuo to give the title compound as a colourless oil (1.007 g)

1. temperatureThe reaction mixture was then heated
2. temperatureat reflux for a further 4 hours
3. temperaturecooled
4. extractionthe solution was extracted successively with ethyl acetate (3×50 mL) and 3:1 chloroform
5. washwashed successively with saturated sodium bicarbonate (50 mL) and brine (50 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customthe solvent evaporated in vacuo
9. dissolutionThe residue was dissolved in dichloromethane
10. custompurified on a silica cartridge (100 g)
11. customover 60 mins
12. additionThe product containing fractions
13. customevaporated in vacuo

ORD record

ord-3897466a9a94443bb406a6c7767e7c94

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754101B2