(3,5-Difluorophenyl)boronic acid → 1-(6-Bromo-4-chloro-3',5'-difluoro-5-methylbiphenyl-2-yl)ethanone

HRID 510891Notes

Reaction equation

[Na].FC(F)(F)S(O[C:8]1[C:13]([C:14](=[O:16])[CH3:15])=[CH:12][C:11]([Cl:17])=[C:10]([CH3:18])[C:9]=1[Br:19])(=O)=O.[F:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[C:27]([F:29])[CH:28]=1>O.C1(C)C=CC=CC=1.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>[Br:19][C:9]1[C:8]([C:25]2[CH:24]=[C:23]([F:22])[CH:28]=[C:27]([F:29])[CH:26]=2)=[C:13]([C:14](=[O:16])[CH3:15])[CH:12]=[C:11]([Cl:17])[C:10]=1[CH3:18]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of sodium hydrogenecarbonate (2.8 g, 34 mmol) in water (70 mL) was added a solution of 6-acetyl-2-bromo-4-chloro-3-methylphenyl trifluoromethanesulfonate (6.7 g, 17 mmol) in toluene (70 mL) followed by (3,5-difluorophenyl)boronic acid (2.9 g, 19 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.98 g, 0.85 mmol). The mixture was bubbled with N2 for 5 min and then heated at 80° C. overnight. The reaction was diluted with water and extracted with ethyl acetate. The combined organic layers were dried, filtered, concentrated and purified on silica gel (eluting with 0-15% of ethyl acetate in hexanes) to give the desired product (5.6 g). LCMS calculated for C15H11BrClF2O (M+H)+: m/z=359.0. found: 359.0.

Workup

customThe mixture was bubbled with N2 for 5 min
additionThe reaction was diluted with water
extractionextracted with ethyl acetate
customThe combined organic layers were dried
filtrationfiltered
concentrationconcentrated
custompurified on silica gel (eluting with 0-15% of ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-b792a0d55301468ea92df5d605c109a2
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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