Iodine → HCID 58266412, compound

Temperature

-20 °C

n-Butyllithium (1.6M in hexanes, 172 mL, 276 mmol) was added to a solution of 2,2,6,6-tetramethylpiperidine (48.5 mL, 285 mmol) in anhydrous THF (200 mL) at −50° C. After 20 min, solid 5-bromo-6-chloronicotinic acid (21.6 g, 92 mmol) was added portionwise and the resultant slurry was allowed to warm to −20° C. over 1 h and stirred at that temperature for 1 h. After this time, the reaction mixture was cooled to −60° C. and transferred via cannula to a solution of iodine (70 g, 276 mmol) in anhydrous THF (100 mL) at −60° C. at such a rate that the internal temperature of the solution remained below −40° C. On complete addition, the reaction mixture was allowed to warm slowly to ambient temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo and the resultant dark red slurry was dissolved in water (500 mL) and washed with diethyl ether (3×200 mL). The pH of aqueous layer was adjusted to 2 by the addition of 1M aqueous hydrochloric acid and the resulting beige precipitate was collected by filtration and dried under vacuum to afford the title compound (17.7 g, 53%). 1H NMR (DMSO-D6, 400 MHz): 8.30 (s, 1H).

1. temperatureAfter this time, the reaction mixture was cooled to −60° C.
2. customremained below −40° C
3. additionOn complete addition
4. temperatureto warm slowly to ambient temperature
5. stirringstirred for 18 h
6. concentrationThe reaction mixture was concentrated in vacuo
7. dissolutionthe resultant dark red slurry was dissolved in water (500 mL)
8. washwashed with diethyl ether (3×200 mL)
9. additionThe pH of aqueous layer was adjusted to 2 by the addition of 1M aqueous hydrochloric acid
10. filtrationthe resulting beige precipitate was collected by filtration
11. customdried under vacuum

ORD record

ord-e0a90c387a294f72ab614d150efdd825

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216980B2