6-(4-Fluorophenyl)-picolinic acid

Uses

Synthesis

21190-87-4

225916-39-2

863704-60-3

General procedure for the synthesis of 6-(4-fluorophenyl)pyridine carboxylic acid from 6-bromo-2-pyridine carboxylic acid and 4-fluorophenylboronic acid neopentyl glycol ester: A) 6-bromopyridine carboxylic acid (2.02 g, 10 mmol) was dissolved in DME containing 4 mL of 10% Na2CO3 aqueous solution under argon protection. To this solution was added Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborolane (2.40 g, 11.5 mmol) and EtOH (20 mL) and the mixture was purged under argon protection. The reaction mixture was heated in a sealed tube at 100 °C for 2.5 hours. After that, additional 6-bromopyridinecarboxylic acid (900 mg) and Pd(OAc)2 were added, and after purging again with argon, heating was continued at 100 °C for 4.5 hours. Upon completion of the reaction, trifluoroacetic acid (20 mL) was added to the mixture, the reaction solution was concentrated and MeOH (150 mL) was added to the residue. The insoluble material was removed by filtration and the filtrate was concentrated. Purification by silica gel fast column chromatography using EtOAc/MeOH (900:100) and EtOAc/MeOH/HOAc (700:1500:50) sequentially as eluents afforded the target product 6-(4-fluorophenyl)pyridinecarboxylic acid (1.0 g, 40% yield, based on borate feedstock) as a white solid.1H NMR (CD3OD) δ 8.01 (d, 1H, J = 7.7 Hz), 7.94-7.87 (m, 3H), 7.73 (d, 1H, J = 7.7 Hz), 7.13 (t, 2H, J = 8.8 Hz); MS (ESI+) m/z 234 (M + H)+.

References