Water → 4-Chloro-3'-fluoro-[1,1'-biphenyl]-3-carboxylic acid

HRID 1771645Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[CH:14][C:15]([Cl:21])=[C:16]([CH:20]=1)[C:17]([OH:19])=[O:18].C([O-])([O-])=O.[Na+].[Na+].O>C(O)C.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.CN(C=O)C>[Cl:21][C:15]1[CH:14]=[CH:13][C:12]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 3-fluorophenyl boronic acid (500 mg, 3.5 mmol, 1.2 eq), 5-bromo-2-chlorobenzoic acid (700 mg, 3.0 mmol, 1.0 eq), Pd(PPh3)4 (687 mg, 0.60 mmol, 0.2 eq) and Na2CO3 (2.52 g, 24 mmol, 8.0 eq) in a mixture of ethanol (5 mL), H2O (5 mL) and DMF (20 mL) was stirred at 100° C. under N2 overnight. The reaction was quenched by addition of diluted HCl (to pH 3) and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4) filtered and evaporated in vacuo. The residue was purified by chromatography (petroleum ether:EtOAc 20:1 to 1:1) to give the title compound as a white solid (500 mg, 67%).

Workup

customThe reaction was quenched by addition of diluted HCl (to pH 3)
extractionthe aqueous phase was extracted with EtOAc
washThe combined organic extracts were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated in vacuo
customThe residue was purified by chromatography (petroleum ether:EtOAc 20:1 to 1:1)

Sources & evidence

ORD record: ord-f006e62019f14ad89187242f92796d37
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

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