Phosphorus oxychloride → Methyl 6-chloropicolinate

Temperature

110 °C

To 6-hydroxy-pyridine-2-carboxylic acid methyl ester (10.0 g, 71.9 mmol) was added phosphorus oxychloride (138 mL). The mixture was heated in an oil bath at 110° C. for 14 h and the excess phosphorus oxychloride was removed in vacuo. The resulting residue was cooled in an ice bath and anhydrous methanol (146 mL) was slowly added. After 15 min, half of the methanol was removed in vacuo and water (208 mL) was added. The solution was cooled in an ice bath and the precipitate was collected. The solid was dissolved in ethyl acetate and this organic phase was washed with water and then a saturated sodium bicarbonate solution. The combined aqueous layers were extracted with ethyl acetate and diethyl ether. The organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo generating 7.47 g (61% yield, 43.5 mmol) of the title compound.

1. customthe excess phosphorus oxychloride was removed in vacuo
2. temperatureThe resulting residue was cooled in an ice bath
3. additionanhydrous methanol (146 mL) was slowly added
4. customhalf of the methanol was removed in vacuo and water (208 mL)
5. additionwas added
6. temperatureThe solution was cooled in an ice bath
7. customthe precipitate was collected
8. dissolutionThe solid was dissolved in ethyl acetate
9. washthis organic phase was washed with water
10. extractionThe combined aqueous layers were extracted with ethyl acetate and diethyl ether
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-99745ca50fdf43969cf9ed30567a54fd

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026244B2