Methanol → Methyl 2,5-Dichloronicotinate

Temperature

0 °C

A solution of 2,5-dichloronicotinic acid (20.2 g, 0.105 mol) in methanol (500 mL) was cooled to 0° C. and neat thionyl chloride (38 mL, 63 g, 0.525 mol) was added over ˜30 min. The reaction mixture was stirred at 0° C. for 1 hour. The cooling bath was removed, the reaction temperature was allowed to warm to room temperature, and the reaction was allowed to stir for an additional 2 days at room temperature. The solvent was removed under reduced pressure to give an off-white residue. The residue was dissolved in Et2O (˜500 mL) and the resulting solution was washed successively with satd. aq. NaHCO3 solution (˜300 mL), water (˜300 mL), and brine (˜300 mL). The organic layer was separated, dried over anhydrous MgSO4, and filtered. Removal of the solvent under reduced pressure yielded methyl 2,5-dichloronicotinate (21.0 g, 97%) as a white solid.

1. customThe cooling bath was removed
2. temperatureto warm to room temperature
3. stirringto stir for an additional 2 days at room temperature
4. customThe solvent was removed under reduced pressure
5. customto give an off-white residue
6. washthe resulting solution was washed successively with satd
7. customThe organic layer was separated
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. customRemoval of the solvent under reduced pressure

ORD record

ord-47238f1ec9374abe80a1a01a0a601b98

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07879838B2