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

HRID 1822345Notes

Reaction equation

HRID 1822345 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.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.[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

7

Reactant 4

HCID 10796Cesium carbonateHCID 11561Benzene, 1-bromo-3-iodo-HCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 13551833Methyl 3-(4-Hydroxy-2-methylphenyl)propanoate

Product 1

HCID 578941923-[4-(3-Bromo-phenoxy)-2-methyl-phenyl]-propionic acid methyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 3-(4-hydroxy-2-methyl-phenyl)-propionic acid methyl ester (5.0 g, 26 mmol), 1-bromo-3-iodobenzene (21.9 g, 77 mmol), copper(I) chloride (1.3 g, 13 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (1.3 mL, 6.5 mmol), and cesium carbonate (12.7 g, 39 mmol) in NMP (100 mL) is heated to 120° C. The reaction is stirred overnight, and then is cooled to room temperature. The reaction is then quenched with 1N aqueous hydrochloric acid and extracted with ethyl ether. The organic is washed with brine, dried over sodium sulfate, filtered, and the solvent is removed. The crude is purified by silica gel column chromatography using 9/1 hexanes/ethyl acetate to elute the pure product. The solvent is removed to afford about 7.86 g (87%) of the desired product. 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calcd for C17H17BrO3 348, found 349 (M+1, 100%).

Workup

  1. customThe reaction is then quenched with 1N aqueous hydrochloric acid
  2. extractionextracted with ethyl ether
  3. washThe organic is washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent is removed
  7. customThe crude is purified by silica gel column chromatography
  8. washto elute the pure product
  9. customThe solvent is removed

Sources & evidence

ORD record
ord-898a8240c2c54d398a23346f086f1109
Source dataset
uspto-grants-2009_10
Patent number
US07608639B2

Reaction notes

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