Methanol → Methyl 2-chloronicotinate

15.0 g (95.2 mmol) of 2-chloronicotinic acid was dissolved in dichloromethane (150 mL), and 8.37 mL (94.5 mmol) of oxalyl chloride was added thereto. Six droplets of N,N-dimethylformamide were added to the above mixture, and the resulting mixture was stirred for 3 hours at room temperature. 40.1 mL (286 mmol) of triethylamine and 37 mL (914 mmol) of methanol were sequentially added dropwise to the above reaction mixture under ice cooling, and the resulting mixture was stirred for 30 minutes under ice cooling. The solvent was distilled off under reduced pressure from the reaction mixture, and then an aqueous solution of sodium hydrogen carbonate was added to the residue. The resulting mixture was extracted with diethyl ether. The organic phase was washed with water, dried, and concentrated, and the residue was purified by column chromatography (ethyl acetate:n-hexane=1:4). 13.9 g of the title compound was obtained as a pale yellow liquid (yield: 86%).

1. stirringthe resulting mixture was stirred for 30 minutes under ice cooling
2. distillationThe solvent was distilled off under reduced pressure from the reaction mixture
3. additionan aqueous solution of sodium hydrogen carbonate was added to the residue
4. extractionThe resulting mixture was extracted with diethyl ether
5. washThe organic phase was washed with water
6. customdried
7. concentrationconcentrated
8. customthe residue was purified by column chromatography (ethyl acetate:n-hexane=1:4)

ORD record

ord-794565eac11b4645a6cf07f67232c4e6

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08334236B2