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

Temperature

-20 °C

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+).

1. temperaturecooled to −70° C.
2. temperatureto warm to 0° C.
3. customquenched with trifluoro-acetic acid(0.57 ml)
4. concentrationconcentrated in vacuo
5. additionadded dropwise to a solution of thionyl chloride (9.77 mL) in MeOH (30 ml) at 0° C
6. temperatureThe reaction mixture was then heated
7. temperatureto reflux for 24 h
8. temperaturecooled to RT
9. concentrationconcentrated in vacuo
10. customThe residue was partitioned between aqueous diluted NaHCO3 and AcOEt
11. customthe layers were separated
12. dry with materialthe organic layer dried over Na2SO4
13. filtrationfiltered
14. customevaporated
15. customthe residue purified by flash chromatography (heptane/AcOEt 1:1)

ORD record

ord-e3f3ea30a7bb45c0a21d61e1a5181e6a

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482341B2