(Pyridin-4-yl)boronic acid → 1-(4-Chloro-3',5'-difluoro-5-methyl-6-pyridin-4-ylbiphenyl-2-yl)ethanone

HRID 510892Notes

Reaction equation

[Na].Br[C:3]1[C:8]([C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=2)=[C:7]([C:17](=[O:19])[CH3:18])[CH:6]=[C:5]([Cl:20])[C:4]=1[CH3:21].[N:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=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>[Cl:20][C:5]1[C:4]([CH3:21])=[C:3]([C:25]2[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=2)[C:8]([C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=2)=[C:7]([C:17](=[O:19])[CH3:18])[CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of sodium hydrogenecarbonate (0.093 g, 1.1 mmol) in water (2 mL) was added a solution of 1-(6-bromo-4-chloro-3′,5′-difluoro-5-methylbiphenyl-2-yl)ethanone (0.20 g, 0.56 mmol) in toluene (2 mL) followed by 4-pyridinylboronic Acid (0.082 g, 0.67 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.033 g, 0.029 mmol). The mixture was bubbled with N2 for 5 min and then heated at 80° C. overnight. The organic layer was concentrated and flashed on silica gel (eluting with 0-35% of ethyl acetate in hexanes) to afford the desired product (13 mg, 6.5%). LCMS calculated for C20H15ClF2NO (M+H)+: m/z=358.1. found: 358.1.

Workup

customThe mixture was bubbled with N2 for 5 min
concentrationThe organic layer was concentrated

Sources & evidence

ORD record: ord-9f30fc5554dc4ec8aa5c01ac3d3bb9ca
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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