Hydrogen Bromide → 5-(3-Chlorophenyl)-3-hydroxy-2-pyridinecarboxylic acid

To a 50 mL round bottom flask adapted for magnetic stirring and fitted with a reflux condenser was charged 5-(3-chlorophenyl)-3-methoxy-2-cyanopyridine, 2, (1 g, 4 mmol) and a 48% aqueous solution of HBr (10 mL). While being stirred, the reaction solution was heated to reflux for 20 hours. The reaction was determined to be complete due to the disappearance of 5-(3-chlorophenyl)-3-methoxy-2-cyanopyridine as measured by TLC analysis using hexane/ethyl acetate (6:3) as the mobile phase and UV 435 nm to visualize the reaction components. The reaction contents was then cooled to 0° C. to 5° C. with stirring and the pH was adjusted to approximately 2 by the slow addition of 50% aqueous NaOH. Stirring was then continued at 0° C. to 5° C. for 3 hours. The resulting solid was collected by filtration and washed with water, then hexane. The resulting cake was dried in vacuo at 40° C. to afford 1.03 g (quantitative yield) of the desired product as an off-white solid. 1H NMR (DMSO-d6) δ 8.52 (d, 1H), 7.99 (d, 1H), 7.95 (s, 1H) 7.81 (t, 1H), 7.57 (s, 1H), and 7.55 (s, 1H).

1. customTo a 50 mL round bottom flask adapted
2. customfitted with a reflux condenser
3. stirringWhile being stirred
4. temperaturethe reaction solution was heated
5. temperatureto reflux for 20 hours
6. customthe reaction components
7. customThe reaction contents
8. temperaturewas then cooled to 0° C. to 5° C.
9. stirringwith stirring
10. stirringStirring
11. filtrationThe resulting solid was collected by filtration
12. washwashed with water
13. customThe resulting cake was dried in vacuo at 40° C.

ORD record

ord-1209e406a0f94eb09f507768d8b1d5b9

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145366B2