Water → 4,5-Dibromopyridine-3-carboxylic acid

Temperature

-55 °C

A cooled (−70° C.) solution of 5-bromonicotinic acid (12.6 g, 62.5 mmol) in THF under nitrogen was treated with 2 M lithium diisopropylamide (72 mL, 144 mmol) dropwise over 1 h. The solution stirred for 2.5 h at −55° C. The mixture was then cooled to −70° C. and treated with 1,2-dibromotetrachloroethane (25 g, 77.2 mmol) in portions over 30 min. After 1 h, the reaction mixture was allowed to warm to −20° C. over 2 h and then water (75 mL) was added slowly. The organic layer was then evaporated in vacuo and the aqueous residue was diluted with water (250 mL), then washed with ethyl acetate. The aqueous layer was then acidified to pH 3 by addition of concentrated hydrochloric acid. The precipitated solid was collected by filtration and dried at 60° C. in vacuo to afford 10 g (57%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.75 (s, 1H), 3.2 (br. s, 1H).

1. temperatureThe mixture was then cooled to −70° C.
2. waitAfter 1 h
3. temperatureto warm to −20° C. over 2 h
4. customThe organic layer was then evaporated in vacuo
5. additionthe aqueous residue was diluted with water (250 mL)
6. washwashed with ethyl acetate
7. additionThe aqueous layer was then acidified to pH 3 by addition of concentrated hydrochloric acid
8. filtrationThe precipitated solid was collected by filtration
9. customdried at 60° C. in vacuo

ORD record

ord-e8795c06217240df9e9138ff1d3f755d

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378104B2