Methanol → Methyl 2-chloro-3-fluoropyridine-4-carboxylate

2-Chloro-3-fluoroisonicotinic acid (3.30 g, 18.8 mmol) was suspended in thionyl chloride (40 ml) and heated under reflux for 2.5 h. The solvent was evaporated and the residue dried by means of azeotropic removal of water with toluene (100 ml) to afford a pale yellow oil. The oil was dissolved in dichloromethane (20 ml) and cooled to 0° C. before methanol (2.42 g, 75.3 mmol) was added dropwise to the solution over 15 min. On complete addition the mixture was allowed to warm to ambient temperature and stirred for 18 h. The solvent was evaporated and the mixture partitioned between water (75 ml) and dichloromethane (100 ml). The aqueous phase was extracted further with dichloromethane (100 ml), the organic layers were combined, washed with brine (75 ml), dried over anhydrous sodium sulphate, filtered and evaporated to give 2-chloro-3-fluoroisonicotinic acid methyl ester (3.32 g, 93%) as a pale yellow solid: δH (360 MHz, CDCl3) 3.99 (3H, s), 7.70 (1H, dd, J 5 and 5), 8.31 (1H, d, J 5).

1. temperatureheated
2. temperatureunder reflux for 2.5 h
3. customThe solvent was evaporated
4. dry with materialthe residue dried by means of azeotropic removal of water with toluene (100 ml)
5. customto afford a pale yellow oil
6. additionwas added dropwise to the solution over 15 min
7. additionOn complete addition the mixture
8. customThe solvent was evaporated
9. customthe mixture partitioned between water (75 ml) and dichloromethane (100 ml)
10. extractionThe aqueous phase was extracted further with dichloromethane (100 ml)
11. washwashed with brine (75 ml)
12. dry with materialdried over anhydrous sodium sulphate
13. filtrationfiltered
14. customevaporated

ORD record

ord-7ddd90cc31fb48abb7e16c882e98708c

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279580B2