Carbon Dioxide → 3,5-Difluorobiphenyl-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Dissolve crude 3,5-difluorobiphenyl (1.3 g, 6.83 mmol) in THF (14 mL) and cool to −78° C. Prepare LiTMP from the addition of BuLi (1.6 M soln in hexanes, 5.33 mL) to tetramethyl piperidine (1.4 mL, 1.25 equiv) at −78° C. in THF (14 mL). Cannulate the cooled LiTMP into the cooled 3,5-difluorobiphenyl and stir the reaction at −78° C. for 1 hour. Bubble carbon dioxide gas through the solution for 5 minutes, warn the reaction to room temperature, pour into 50 mL of 1M NaOH, and extract with 50 mL EtOAc. Discard the organic layer. Acidify the remaining aqueous layer with conc. HCl and extract twice with EtOAc. Dry the organics over MgSO4, filter, and evaporate to give 1.22 g of the title compound as a white solid (77%). MS (ES): m/z 233.1 (M−H).

Provenance & Evidence