Hydrochloric Acid → 5-(3,5-Difluorophenyl)-2,3-dimethyl-benzoic acid

HRID 1771822Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[C:18]([F:20])[CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].Cl>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.CN(C=O)C>[F:13][C:14]1[CH:15]=[C:16]([C:2]2[CH:3]=[C:4]([CH3:12])[C:5]([CH3:11])=[C:6]([CH:10]=2)[C:7]([OH:9])=[O:8])[CH:17]=[C:18]([F:20])[CH:19]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 5-bromo-2,3-dimethylbenzoic acid (500 mg, 2.18 mmol, 1.0 eq), (3,5-difluorophenyl)boronic acid (414 mg, 2.62 mmol, 1.2 eq) and Na2CO3 (925 mg, 8.73 mmol, 4.0 eq) in a mixture of EtOH (5 mL), DMF (20 mL) and water (5 mL) was added Pd(PPh3)4 (252 mg, 0.22 mmol, 0.1 eq) under nitrogen. The mixture was stirred at 100° C. overnight. Water was added and the mixture acidified to pH 3 by addition of 3M HCl. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (CH2Cl2:MeOH, 300:1 to 200:1) to give the title compound as a white solid (184 mg, 32%).

Workup

extractionThe aqueous layer was extracted with EtOAc
washthe combined organic extracts were washed with water and brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated in vacuo
customThe residue was purified by column chromatography (CH2Cl2:MeOH, 300:1 to 200:1)

Sources & evidence

ORD record: ord-18dd00cabe0a4d0f8769ab4681d84b44
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

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