Dimethylformamide → 3-(3-Fluorophenyl)-5-methyl-benzoic acid

HRID 1771752Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([OH:7])=[O:6].[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=2)[C:5]([OH:7])=[O:6])[CH:16]=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 3-bromo-5-methylbenzoic acid (3.0 g, 13.95 mmol, 1.0 eq), 3-fluorophenylboronic acid (2.34 g, 16.74 mmol, 1.2 eq) and Na2CO3 (5.91 g, 55.8 mmol, 4.0 eq) in a mixture of EtOH (10 mL), DMF (40 mL) and H2O (10 mL) was added Pd(PPh3)4 (806 mg, 0.7 mmol, 0.05 eq). The mixture was stirred at 100° C. overnight. Water was added and the aqueous layer extracted with EtOAc. The organic extract was discarded and the aqueous layer was acidified to pH 4-5 by addition of 1M HCl. The aqueous layer was extracted with EtOAc and the combined organic extracts were filtered through silica gel and concentrated to give the title compound as a white solid (2.0 g, 62%)

Workup

extractionthe aqueous layer extracted with EtOAc
extractionThe organic extract
additionthe aqueous layer was acidified to pH 4-5 by addition of 1M HCl
extractionThe aqueous layer was extracted with EtOAc
filtrationthe combined organic extracts were filtered through silica gel
concentrationconcentrated

Sources & evidence

ORD record: ord-2055df444094495598325307e83e933c
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

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