Carbon Dioxide → 4-chloro-5-fluoropyridine-3-carboxylic acid

Temperature

-78 °C

N-Butyllithium, 1.6 M in hexanes (9.50 mL, 15.21 mmol) was added to THF (20 mL) and cooled to −78° C. To this solution was added diisopropylamine (2.167 mL, 15.21 mmol) followed by 4-chloro-3-fluoropyridine (2 g, 15.21 mmol) and the solution stirred for 6 h at −78° C. The reaction mixture was then poured on to crushed dry ice and stirred until the reaction mixture warmed to room temperature. The reaction was quenched by addition of aqueous ammonium chloride solution and acidified to pH=2 using conc. HCl and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulphate and concentrated under reduced pressure to afford the 4-chloro-5-fluoronicotinic acid (1.7 g, 9.68 mmol, 64% yield) as a pale yellow solid. LCMS (ESI) m/e 175.9 [(M+H)+, calcd for C6H4ClFNO2 176.0]; LC/MS retention time (Method F): tR=0.57 min.

1. additionThe reaction mixture was then poured on
2. stirringstirred until the reaction mixture
3. temperaturewarmed to room temperature
4. customThe reaction was quenched by addition of aqueous ammonium chloride solution
5. extractionextracted with ethyl acetate (3×10 mL)
6. washThe combined organic layers were washed with brine (10 mL)
7. dry with materialdried over sodium sulphate
8. concentrationconcentrated under reduced pressure

ORD record

ord-e35d10e482294884867fd793ee0f6d8f

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969564B2