Water → Methyl 3-chloro-5-methoxypicolinate

Temperature

55 °C

In a 1-L flask, methyl 3-chloro-5-hydroxypicolinate (Afferchem, 25.00 g, 133 mmol) and cesium carbonate (87 g, 267 mmol) were suspended in DMF (200 mL) and iodomethane (41.7 mL, 666 mmol) was added dropwise. A water-cooled condenser was attached, and the reaction vessel was heated in a 55° C. oil bath. After 3 h the reaction was concentrated under reduced pressure. The residue was taken up in 1.2 L of 80% EtOAc-hexane and 500 mL brine. The mixture was filtered through Celite. The filtrate was transferred into a separation funnel. The organic layer was separated, washed with brine (100 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 30% to 40% EtOAc-hexane, affording the title compound (19.1 g) as a tan solid. MS m/z=202 (M+H).

1. concentrationAfter 3 h the reaction was concentrated under reduced pressure
2. filtrationThe mixture was filtered through Celite
3. customThe filtrate was transferred into a separation funnel
4. customThe organic layer was separated
5. washwashed with brine (100 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography
9. washeluting with 30% to 40% EtOAc-hexane

ORD record

ord-787d0beb0c0641d0a4c4b065d9bc6eab

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2