Ethanol → 6-(4-Fluorophenyl)picolinic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 6-bromopicolinic acid (Aldrich) (2.02 g, 10 mmol) in DME containing 4 mL of 10% aq Na2CO3 was purged with Ar gas. To this mixture was added Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane (2.40 g, 11.5 mmol, Wako Pure Chemical Industries, Ltd) and EtOH (20 mL), and the mixture was purged with Ar gas. The reaction mixture was heated at 100° C. for 2.5 h in a sealed tube. Additional 2-bromopicolinic acid (900 mg) and Pd (OAc)2 was added, and after purging with Ar gas it was heated at 100° C. for 4.5 h. Trifluoroacteic acid (20 mL) was added to the reaction mixture, concentrated and MeOH (150 mL) was added to the residue. The insoluble material was filtered, and the filtrate solution was concentrated. Purification by flash column on silica gel eluting with EtOAc/MeOH//900:100 followed by EtOAc/MeOH/HOAc//700:1500:50 provided the desired product (1.0 g, 40% based on borinane starting material) 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, 8.8 Hz); MS(ESI+) m/z 234 (M+H)+.

Provenance & Evidence