Hydrochloric Acid → Methyl 2-chloro-6-(methylamino)isonicotinate

Temperature

65 °C

To a solution of 2-chloro-6-(methylamino)isonicotinic acid (18.1 g, 97 mmol) in 600 mL MeOH was added thionyl chloride (7.783 mL, 107 mmol) very slowly (emits HCl gas violently). Reaction refluxed to 65° C. for 2 h. After 2 h, reaction was concentrated in vacuo. The residue was dissolved in EtOAc (400 mL) and neutralized with saturated NaHCO3 solution (300 mL). The aqueous solution was extracted with EtOAc (150 mL×3). The combined organics were washed with brine (150 mL), dried over Mg2SO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (5% EtOAc/hexanes, then 20% EtOAc/hexanes) yielded 11.3 g (58%) of methyl 2-chloro-6-(methylamino)isonicotinate as a yellow brown solid. 1H NMR (CDCl3, 400 mHz) 7.08 (d, J=0.91 Hz, 1H); 6.84 (d, J=0.73 Hz, 1H); 5.09 (s, NH); 3.92 (s, 3H); 2.96 (d, J=5.31 Hz, 3H); LC/MS [M+H]+=201.0.

1. customReaction
2. customreaction
3. concentrationwas concentrated in vacuo
4. dissolutionThe residue was dissolved in EtOAc (400 mL)
5. extractionThe aqueous solution was extracted with EtOAc (150 mL×3)
6. washThe combined organics were washed with brine (150 mL)
7. dry with materialdried over Mg2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification by normal phase chromatography (5% EtOAc/hexanes

ORD record

ord-b74d18a44ce542d6a5cc514477489715

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394837B2