Cesium carbonate → 3-[4-(3-Bromo-5-fluoro-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester

HRID 1822266Notes

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[C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([Br:23])[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:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([Br:23])[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), 1,3-dibromo-5-fluorobenzene (15.71 g, 61.9 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 7 hours under N2. The reaction is cooled and quenched with 1 N HCl (40 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 3.43 g (45%) of the title compound. Rf=0.38 (4/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C17H16O3BrF 366, found 384 and 386 (M+NH4, 100%).

Workup

temperatureThe reaction is cooled
customquenched with 1 N HCl (40 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-a8058d2f69ed484b8c2f0b40bdda27f9
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608639B2

Reaction notes

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