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

Dissolve crude 3,5-difluorbiphenyl (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 h. Bubble carbon dioxide gas through the solution for 5 minutes, warm the reaction to rt, pour into 50 mL of 1M NaOB, and extract with 50 mL EtOAc. Discard the organic layer was discarded. Acidify the remaining aqueous layer with conc. HCl and extract twice with EtOAc. Dry the organics over MgSO4, filtered, and evaporate to give 1.22 g of the title compound as a white solid (77%). MS (m/e): 233.1 (M−).

1. temperaturecool to
2. custom−78° C
3. customthe reaction at −78° C. for 1 h
4. temperaturewarm
5. customthe reaction to rt
6. additionpour into 50 mL of 1M NaOB
7. extractionextract with 50 mL EtOAc
8. extractionAcidify the remaining aqueous layer with conc. HCl and extract twice with EtOAc
9. dry with materialDry the organics over MgSO4
10. filtrationfiltered
11. customevaporate

ORD record

ord-91a66127e69f454ebb20ae79a1a0f2f3

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07326731B2