Methanol → Methyl 3-aminopicolinate

Temperature

-78 °C

A solution of 3-aminopyridine-2-carbonitrile (9.7 g, 81.8 mmol) in MeOH (100 mL) was placed in a round bottom pressure vessel. The solution was cooled to −78° C. and HCl gas was bubbled through the solution until the volume of the solution had noticeably increased. The flask was sealed and the reaction warmed to room temperature and stirred overnight. At this time, LCMS (sampled after re-cooling the reaction to −78° C.) showed only a small amount of starting cyano compound remaining. Water (14 mL, 818 mmol) was added and the reaction transferred to a flask equipped with a reflux condenser. The reaction was refluxed overnight. The solution was concentrated and the remaining solution was basified with 1N NaOH to pH 9, then extracted with CHCL3 repeatedly until very little UV-active material was removed. The organic layers were dried over Na2SO4, filtered and evaporated to give the product as a pink solid.

1. customHCl gas was bubbled through the solution until the volume of the solution
2. temperaturehad noticeably increased
3. customThe flask was sealed
4. temperaturethe reaction warmed to room temperature
5. aliquotAt this time, LCMS (sampled
6. temperatureafter re-cooling
7. customthe reaction to −78° C.)
8. customthe reaction transferred to a flask
9. customequipped with a reflux condenser
10. temperatureThe reaction was refluxed overnight
11. concentrationThe solution was concentrated
12. extractionextracted with CHCL3 repeatedly until very little UV-active material
13. customwas removed
14. dry with materialThe organic layers were dried over Na2SO4
15. filtrationfiltered
16. customevaporated

ORD record

ord-cc6c432b76324419a021c39bcb122269

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279487B2