Carbon Dioxide → 3,5-Difluorobiphenyl-4-carboxylic acid
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[Li]N1C(C)(C)CCCC1(C)C.[Li]CCCC.CC1CCCN(C)C1(C)C.[C:41](=[O:43])=[O:42].[OH-].[Na+]>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[C:6]([F:8])[C:7]=1[C:41]([OH:43])=[O:42]Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
Dissolve crude 3,5-difluorobiphenyl (1.3 g, 6.83 mmol) in tetrahydrofuran (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 tetrahydrofuran (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, warm the reaction to room temperature, pour into 50 mL of 1M sodium hydroxide, and extract with 50 mL ethyl acetate. Discard the organic layer. Acidify the remaining aqueous layer with conc. HCl and extract twice with ethyl acetate. Dry the organics over magnesium sulfate, filtered, and evaporate to give 1.22 g of the title compound as a white solid (77%). MS (m/e): 233.1 (M−).
Workup
- customthe reaction at −78° C. for 1 hour
- temperaturewarm
- customthe reaction to room temperature
- extractionextract with 50 mL ethyl acetate
- extractionextract twice with ethyl acetate
- dry with materialDry the organics over magnesium sulfate
- filtrationfiltered
- customevaporate
Sources & evidence
- ORD record
- ord-b5d93b37e60b4eea83e73aaaf9864d9c
- Source dataset
- uspto-grants-2007_09
- Patent number
- US07265246B2
Reaction notes
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