Cesium carbonate → Methyl 4'-chloro-2-methyl[1,1'-biphenyl]-4-carboxylate
Reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[C:6]([CH3:11])[CH:5]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]([C:4]1[CH:9]=[CH:8][C:7]([C:17]2[CH:18]=[CH:19][C:14]([Cl:13])=[CH:15][CH:16]=2)=[C:6]([CH3:11])[CH:5]=1)=[O:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
A mixture of 250 mg (1.09 mmol) of 4-bromo-3-methyl-benzoic acid methyl ester, 204 mg (1.31 mmol) of 4-chlorophenylboronic acid, 1.06 g (3.27 mmol) of cesium carbonate (Cs2CO3) and PdCl2(dppf) catalyst (5 mol %) was flushed with argon. To this mixture was added 3 mL of 1,4-dioxane and the reaction mixture was heated to 80° C. overnight. The mixture was then cooled to rt, and filtered through a pad of Celite while rinsing the pad with ethyl acetate. The filtrate was washed with brine, dried over sodium sulfate and concentrated to give a residue which was chromatographed on silica gel (5% ethyl acetate in hexane) to afford 191 mg (67%) of desired 4′-chloro-2-methyl-biphenyl-4-carboxylic acid methyl ester, as an oil as indicated by 1H NMR; LC-MS calcd for C15H13ClO2 [M++H]+: 261.07, found: 261.1.
Workup
- customwas flushed with argon
- additionTo this mixture was added 3 mL of 1,4-dioxane
- temperatureThe mixture was then cooled to rt
- filtrationfiltered through a pad of Celite
- washwhile rinsing the pad with ethyl acetate
- washThe filtrate was washed with brine
- dry with materialdried over sodium sulfate
- concentrationconcentrated
- customto give a residue which
- customwas chromatographed on silica gel (5% ethyl acetate in hexane)
Sources & evidence
- ORD record
- ord-a6cbb640816145b6943803ec401ba4cb
- Source dataset
- uspto-grants-2008_11
- Patent number
- US07449488B2
Reaction notes
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