Potassium Carbonate → 3-Pyridazin-4-yl-4'-(trifluoromethyl)biphenyl-4-ol

HRID 1619627Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[CH:14]=[CH:13][N:12]=[N:11][CH:10]=2)[CH:3]=1.[F:15][C:16]([F:27])([F:26])[C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.Cl.[Cl-].[Na+].O.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[N:12]1[CH:13]=[CH:14][C:9]([C:4]2[CH:3]=[C:2]([C:20]3[CH:21]=[CH:22][C:17]([C:16]([F:27])([F:26])[F:15])=[CH:18][CH:19]=3)[CH:7]=[CH:6][C:5]=2[OH:8])=[CH:10][N:11]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-chloro-2-pyridazin-4-ylphenol (Preparation 7, 1.5 g, 7.26 mmol) and 4-trifluoromethylbenzene boronic acid (3.45 g, 18.1 mmol) in 1,4-dioxane (20 mL) was added a solution of potassium carbonate (2.0 g, 14.5 mmol) in water (4 mL). The reaction mixture was degassed, then bis(tri-t-butylphosphine) palladium (0) (371 mg, 0.726 mmol) added and the reaction mixture heated to 100° C. for 18 hours. The mixture was diluted with a 2M aqueous solution of hydrogen chloride and brine, then extracted with ethyl acetate. The organic layer was separated and dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (0%-100% ethyl acetate in dichloromethane gradient elution) to afford the title compound as a solid (940 mg, 41%).

Workup

customThe reaction mixture was degassed
extractionextracted with ethyl acetate
customThe organic layer was separated
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography (0%-100% ethyl acetate in dichloromethane gradient elution)

Sources & evidence

ORD record: ord-02938912a8d8433d9cf3f6613adbdd96
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772293B2

Reaction notes

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