Phosphorus oxychloride → Methyl 6-chloro-5-isobutoxynicotinate

To 3-isobutoxy-5-(methoxycarbonyl)pyridine 1-oxide (7.04 g) was added phosphoryl chloride (25 mL), and the mixture was heated under reflux for 30 min. The solvent in the reaction mixture was evaporated under reduced pressure, and saturated aqueous sodium hydrogen carbonate solution was added at 0° C. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give a crude product of the title compound (3.18 g) as a white amorphous solid. This compound was used for the next step without further purification.

1. temperaturethe mixture was heated
2. temperatureunder reflux for 30 min
3. customThe solvent in the reaction mixture was evaporated under reduced pressure, and saturated aqueous sodium hydrogen carbonate solution
4. additionwas added at 0° C
5. extractionThe reaction mixture was extracted with ethyl acetate
6. washthe extract was washed with water and saturated brine
7. dry with materialdried over anhydrous magnesium sulfate
8. customThe solvent was evaporated under reduced pressure
9. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

ORD record

ord-5ec068f77a31448f8c8943435a413ef6

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181186B2