Methane → HCID 10992645, compound

Temperature

105 °C

Propyl amine (110 g, 0.3407 mol), triethyl amine (194 ml, 140.8 g, 1.39 moles) and methyl 2-chloronicotinate-HCl (84.6 g, 0.408 mol) were dissolved in toluene (380 ml) contained in a 1 liter 3 neck roundbottom flask stirred with a mechanical stirrer and equipped with nitrogen. The mixture was heated to 105° C. for 60 hours. After cooling to room temperature, ethyl acetate (500 ml) and sodium bicarbonate (5% aq., 500 ml) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×200 ml). The combined organic layers were washed with water (500 ml). The organic solution was concentrated under reduced pressure to give a dark viscous oil. This oil was dissolved in pyridine (300 ml, 3.71 mol) and the solution was placed in a 1 liter 3 neck roundbottom flask equipped with a magnetic stirrer. Then phosphorous oxychloride (68 ml, 0.73 mol) was added. The mixture was heated to 75° C. for about 3 hours. After cooling to 5° C., the mixture was carefully diluted with ethyl acetate (500 ml). Sodium hydroxide (1N in water, 120 ml) was then slowly added. The organic layer was separated. The aqueous layer was extracted with ethyl acetate (2×300 ml). The organic layers were combined and washed with sodium hydroxide (1N in water, 2×50 ml) and water (100 ml). Concentration under vacuum, followed by concentration from toluene solution (2×150 ml), gave a dark brown oil. This oil was dissolved in methanol (330 ml) and activated charcoal (5 g) was added. The mixture was heated to reflux for 15 minutes and filtered hot through Celite. The filtrate was cooled to room temperature and stirred for 24 hours. The resulting solid was filtered, washed with methanol and dried under vacuum to give the desired product as an off-white solid.

1. customequipped with nitrogen
2. temperatureAfter cooling to room temperature
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×200 ml)
5. washThe combined organic layers were washed with water (500 ml)
6. concentrationThe organic solution was concentrated under reduced pressure
7. customto give a dark viscous oil
8. customequipped with a magnetic stirrer
9. temperatureThe mixture was heated to 75° C. for about 3 hours
10. temperatureAfter cooling to 5° C.
11. customThe organic layer was separated
12. extractionThe aqueous layer was extracted with ethyl acetate (2×300 ml)
13. washwashed with sodium hydroxide (1N in water, 2×50 ml) and water (100 ml)
14. concentrationConcentration under vacuum
15. concentrationfollowed by concentration from toluene solution (2×150 ml)
16. customgave a dark brown oil
17. temperatureThe mixture was heated
18. temperatureto reflux for 15 minutes
19. filtrationfiltered hot through Celite
20. temperatureThe filtrate was cooled to room temperature
21. stirringstirred for 24 hours
22. filtrationThe resulting solid was filtered
23. washwashed with methanol
24. customdried under vacuum

ORD record

ord-010583068caf45089642cc7d1e87f34e

Source dataset

uspto-grants-1994_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05284954