Carbon Dioxide → Methyl 2-(6-aminopyridin-2-yl)acetate

Participants

Reaction Conditions

Reaction Steps

1,1,1,3,3,3-Hexamethyl-2-(6-methyl-pyridin-2-yl)-disilazane (1.7 g) under an argon atmosphere in THF (20 mL) was cooled to −20° C. and treated dropwise at −20° C. with 6.73 mL of a 2 M solution of lithium diisopropylamide in THF/heptane/ethylbenzene (Fluka). The solution was stirred 1 h at −20° C., cooled to −70° C. and then treated with an access of dry ice. The mixture was allowed to warm to 0° C. and then quenched with trifluoro-acetic acid(0.57 ml) and concentrated in vacuo. The residue was taken up in MeOH and added dropwise to a solution of thionyl chloride (9.77 mL) in MeOH (30 ml) at 0° C. The reaction mixture was then heated to reflux for 24 h, cooled to RT and concentrated in vacuo. The residue was partitioned between aqueous diluted NaHCO3 and AcOEt, the layers were separated, the organic layer dried over Na2SO4, filtered, evaporated and the residue purified by flash chromatography (heptane/AcOEt 1:1) to give (6-amino-pyridin-2-yl)-acetic acid methyl ester as a crystalline off-white solid (0.429 g). MS (EI): 166.0 (M+).

Provenance & Evidence