Phenol → HCID 57894208, compound

HRID 1822294Notes

Reaction equation

HRID 1822294 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=3Br)[CH:15]=2)=[CH:9][C:8]=1[CH3:33])[CH3:2].[C:35]1([OH:41])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1CCCC1=O.[Cu]Cl>[CH2:1]([O:3][C:4](=[O:34])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:15]=[C:16]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=3[O:41][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:17]=[C:18]([CH3:20])[CH:19]=2)=[CH:9][C:8]=1[CH3:33])[CH3:2]

Participants

7

Reactant 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 57894173HCID 57894173, compound

Product 1

HCID 57894208HCID 57894208, compoundYield 54.6%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 3-{4-[3-(2-bromo-4-trifluoromethyl-phenoxy)-5-methyl-phenoxy]-2-methyl-phenyl}-propionic acid ethyl ester (0.309 g, 0.576 mmol), phenol (0.163 g, 1.73 mmol), cesium carbonate (0.56 g, 1.72 mmol), copper (I) chloride (0.029 g, 0.293 mmol) and 2,2,6,6-tetramethyl-3,5-heptanedione (0.027 g, 0.147 mmol) in 1-methyl-2-pyrrolidinone (10 mL) is heated to 120° C. for 20 hours under N2. The reaction is cooled and quenched with 1 N HCl (20 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 0.173 g (43%) of the title compound. Rf=0.55 (4/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) M/z mass calculated for C32H29O35F3 550, found 551 (M+1, 100%).

Workup

  1. temperatureThe reaction is cooled
  2. customquenched with 1 N HCl (20 mL)
  3. additionThe mixture is then diluted with Et2O
  4. extractionextracted with water
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. customthe solvent is removed in vacuo
  7. customto afford crude product that
  8. customis absorbed on silica gel
  9. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c48688ead529439ab9bd49708feeb1d1
Source dataset
uspto-grants-2009_10
Patent number
US07608639B2

Reaction notes

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