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

HRID 1822319Notes

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](Br)[C:17]=1[CH3:23].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])[C:17]=2[CH3:23])=[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 (2.0 g, 10.3 mmol), 2,6-dibromotoluene (7.72 g, 30.9 mmol), cesium carbonate (4.03 g, 12.4 mmol), and 2,2,6,6-tetramethyl-3,5-heptanedione (0.47 g, 2.55 mmol) in 1-methyl-2-pyrrolidinone (20 mL) is purged with N2, and then copper (I) chloride (0.51 g, 5.15 mmol) is added. The reaction is heated to 120° C. for 17 hours under N2, and then cooled and quenched with 1 N HCl (50 mL). The mixture is diluted with water and extracted with Et2O. 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 2.92 g (78%) of the title compound. Rf=0.35 (4/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C18H19O3Br 362, found 363 and 365 (M+1 and M+3, 100%).

Workup

customis purged with N2
temperaturecooled
customquenched with 1 N HCl (50 mL)
additionThe mixture is diluted with water
extractionextracted with Et2O
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-36beed97a8224dca8cab09bf075cf82d
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608639B2

Reaction notes

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