Methanol → Methyl 5-chloro-3-methoxypicolinate

Temperature

0 °C

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 purified 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).

1. customThe vessel was sealed
2. temperatureheated to 95° C. for 1.5 h
3. temperatureThe reaction mixture was cooled to 0° C.
4. customquenched with Na2CO3 (1M, 140 mL)
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. extractionthe residue was extracted with EtOAc (3×100 mL)
7. dry with materialThe combined organics extracts were dried over MgSO4
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography (gradient 20%-33% EtOAc/hexane)

ORD record

ord-656146e2fb2347acb30076a9dc5b3057

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2