Hydrochloric Acid → 5-Chloropyrazinoic acid

Temperature

37.5 °C

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added methyl 5-chloropyrazine-2-carboxylate (1.0 eq) and tetrahydrofuran (4.92 vols) under a nitrogen atmosphere. The reaction mixture was agitated until all the solid had dissolved, then filtered into a second flask. Water (8.65 vols) was added to the reaction mixture and the mixture agitated for approximately 15 minutes. Potassium carbonate (2.1 eq) was added to the reaction mixture and the mixture agitated for 16 hours at 20-25° C. Then 32% w/w hydrochloric acid (3.76 eq) was added over 3 hours in small portions, keeping the reaction temperature 20-25° C., to a pH end point of pH2.2. The resultant slurry was heated to approximately 35-40° C. and then distilled under vacuum at this temperature distilling approximately 5.3 vols, to a final volume of approximately 9.3 vols. The mixture was then cooled to 20-25° C. over at least 2 hours, agitated for 10 hours at this temperature and then filtered. The solid was washed with water (2.8 vols), and the wet product produced dried at 35° C. in a vacuum oven. The desired product was obtained as a solid (corrected yield 91%) 1H NMR δ (400 MHz CDCl3): 7.20 (1H, bs), 8.72 (1H, s), 9.21-9.21 (1H, m); m/z 157 (M−H)+.

1. customTo a flask fitted with overhead stirrer, condenser
2. dissolutionhad dissolved
3. filtrationfiltered into a second flask
4. additionWater (8.65 vols) was added to the reaction mixture
5. stirringthe mixture agitated for approximately 15 minutes
6. stirringthe mixture agitated for 16 hours at 20-25° C
7. customthe reaction temperature 20-25° C.
8. distillationdistilled under vacuum at this temperature
9. distillationdistilling approximately 5.3 vols
10. temperatureThe mixture was then cooled to 20-25° C. over at least 2 hours
11. stirringagitated for 10 hours at this temperature
12. filtrationfiltered
13. washThe solid was washed with water (2.8 vols)
14. customthe wet product produced
15. customdried at 35° C. in a vacuum oven

ORD record

ord-c39d140b8cea42088c711812501abf1f

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093252B2