Cesium carbonate → 3-[4-(3-Bromo-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester

HRID 1822256

Reaction equation

[CH3:1][O:2][C:3](=[O:14])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[CH3:13].[Br:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18](I)[CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1CCCC1=O.[Cu]Cl>[CH3:1][O:2][C:3](=[O:14])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([Br:15])[CH:17]=2)=[CH:8][C:7]=1[CH3:13]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-(4-hydroxy-2-methyl-phenyl)-propionic acid methyl ester (4.0 g, 20.6 mmol), 1-bromo-3-iodobenzene (17.49 g, 61.8 mmol), cesium carbonate (8.05 g, 24.7 mmol), copper (I) chloride (1.02 g, 10.3 mmol) and 2,2,6,6-tetramethyl-3,5-heptanedione (0.95 g, 5.15 mmol) in 1-methyl-2-pyrrolidinone (40 mL) is heated to 120° C. for 17 hours under N2. The reaction is cooled and quenched with 1 N HCl (50 mL). The mixture is then diluted with Et2O and extracted with water. The organic layer is dried (Na2SO4), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 9/1 hexanes/ethyl acetate to afford 4.30 g (60%) of the title compound. Rf=0.33 (4/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C17H17O3Br 348, found 349 and 351 (M+1 and M+3, 100%).

Workup

temperatureThe reaction is cooled
customquenched with 1 N HCl (50 mL)
additionThe mixture is then diluted with Et2O
extractionextracted with water
dry with materialThe organic layer is dried (Na2SO4)
customthe solvent is removed in vacuo
customto afford crude product that
customis absorbed on silica gel
custompurified by flash chromatography

Sources & evidence

ORD record: ord-50ada645cd54442197b4edc8fc39a3e6
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608639B2

Linked notes

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