Hydrochloric Acid → HCID 4140883, compound

Temperature

-5 °C

2-Chloronicotinic acid (2.5 grams, 15.9 mmol) and 80 ml THF is placed in a 250 ml three neck round bottom flask equipped with mechanical stirring, a thermometer and a rubber septum with a nitrogen inlet. The reaction mixture is cooled to -5° C. and N-methylmorpholine (1.6 grams, 15.9 mmol) added via syringe. Isobutyl chloroformate (2.2 grams, 15.9 mmol) is then added via syringe while maintaining the temperature below 0° C. The reaction is stirred for 30 minutes at -5° C. The p-fluorobenzylamine (2.2 grams, 17.5 mmols) is then added via syringe, keeping the temperature below 0° C. The reaction is allowed to warm to room temperature and stirred for 18 hours, after which 1M HCl (30 ml) is added. This is then extracted with ethyl acetate (2×30 ml), and the combined organics washed with 1M HCl (1×30 ml), 3M NaOH (2×30 ml), H2O (1×50 ml) and brine (1×50 ml). The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated to a yellow solid. This is triturated with diethyl ether, filtered, washed with fresh diethyl ether and dried in vacuo to yield 3.4 g (80.5%) of the desired chloronicotinamide as a white crystalline solid.

1. customequipped with mechanical stirring
2. temperaturewhile maintaining the temperature below 0° C
3. customthe temperature below 0° C
4. temperatureto warm to room temperature
5. stirringstirred for 18 hours
6. extractionThis is then extracted with ethyl acetate (2×30 ml)
7. washthe combined organics washed with 1M HCl (1×30 ml), 3M NaOH (2×30 ml), H2O (1×50 ml) and brine (1×50 ml)
8. dry with materialThe organic layer is dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated to a yellow solid
11. customThis is triturated with diethyl ether
12. filtrationfiltered
13. washwashed with fresh diethyl ether
14. customdried in vacuo

ORD record

ord-e433567037bf4d25ac5970c8e00376dc

Source dataset

uspto-grants-1989_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04861891