Methanol → Methyl 5-chloro-3-methoxypicolinate

Participants

Reaction Conditions

Reaction Steps

In a 350-mL resealable vessel, 5-chloro-3-methoxypicolinic acid (intermediate 14, 7.51 g, 40.0 mmol) was dissolved in MeOH (120 mL). The solution was cooled to 0° C., and concentrated sulfuric acid (7.57 mL, 140 mmol) was added. The vessel was sealed and heated to 95° C. for 1.5 h. The reaction mixture was cooled to 0° C., and quenched with Na2CO3 (1M, 140 mL). The reaction mixture was concentrated under reduced pressure and the residue was extracted with EtOAc (3×100 mL). The combined organics extracts were dried over MgSO4 and the filtrate was concentrated under reduced pressure. The residue was by silica gel chromatography (gradient 20%-33% EtOAc/hexane) to afford the title compound as a yellow solid (5.59 g, 27.7 mmol, 67%). MS m/z=202 [M+H]+. Calculated for C8H8ClNO3: 201. 1H NMR in CDCl3 δ: 8.24 (d, 1H, J=1.9), 7.37 (d, 1H, J=1.9), 3.97 (s, 3H), 3.94 (s, 3H).

Provenance & Evidence