Potassium Carbonate → 3-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester

HRID 1665241Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=2)[CH:5]=1.[F:21][C:22]1[C:27]([F:28])=[CH:26][C:25](B(O)O)=[C:24]([O:32][CH3:33])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([C:25]3[CH:26]=[C:27]([F:28])[C:22]([F:21])=[CH:23][C:24]=3[O:32][CH3:33])=[CH:15][CH:14]=2)[CH:5]=1

Participants

Conditions

Temperature: 45 °C

Procedure

To a mixture of 4-fluoro-3-(4-iodophenoxy)methylbenzoic acid methyl ester (1.1 g, 2.85 mmol) and 4,5-difluoro-2-methoxyphenylboronic acid (0.642 g, 3.4 mmol) in DMF (15 mL) and water (2.5 mL) was added Pd(dppf)Cl2 (220 mg, 0.27 mmol) and potassium carbonate (1.24 g, 9.0 mmol). The mixture was stirred at 45° C. overnight and solvents were evaporated. The residue was extracted with ethyl acetate and water. The organic layer was dried and concentrated. The residue was purified through flash column chromatography (120 g silica gel, 5% to 40% ethyl acetate in hexanes over 25 minutes) to give a white solid as 3-(4′,5′-difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester (0.76 g, 67%).

Workup

customsolvents were evaporated
extractionThe residue was extracted with ethyl acetate and water
customThe organic layer was dried
concentrationconcentrated
customThe residue was purified through flash column chromatography (120 g silica gel, 5% to 40% ethyl acetate in hexanes over 25 minutes)

Sources & evidence

ORD record: ord-63e2b9ac7335416a8d92a5de3f607588
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039495B2

Reaction notes

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