Phenol → HCID 86607510, compound

HRID 2368725Notes

Reaction equation

HRID 2368725 reaction equation
Br[C:2]1[S:6][C:5]([CH:7]=[O:8])=[C:4]([CH3:9])[CH:3]=1.[C:10]1([OH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C1(C)C=CC=CC=1.ClCCl.[OH-].[Na+]>[CH3:9][C:4]1[CH:3]=[C:2]([O:16][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[S:6][C:5]=1[CH:7]=[O:8]

Participants

8

Reactant 4

HCID 996PhenolHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 151154075-Bromo-3-methylthiophene-2-carbaldehyde

Product 1

HCID 86607510HCID 86607510, compoundYield 19.5%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 5-bromo-3-methyl-thiophene-2-carbaldehyde (example 1.a, 30.8 g, 150 mmol), phenol (28.2 g, 300 mmol), cesium carbonate (97 g, 300 mmol), copper(I) trifuoromethanesulfonate benzene complex (90%, 7.5 g, 15 mmol), and ethyl acetate (750 μL, 7.5 mmol) in 150 mL of anhydrous toluene was heated at reflux temperature for 48 hours. The resultant mixture was diluted with dichloromethane and 2 N NaOH(aq) and filtered through a small pad of celite, the solid was washed with additional dichloromethane and NaOH solution. The biphasic mixture was separated and the organic fraction was successively washed with 2 N NaOH and brine. The organic fraction was dried over anhydrous magnesium sulfate and concentrated to a residue. The crude product was purified by column chromatography, eluting the desired product from silica gel with a gradient of 5-30% ethyl acetate in hexanes to provide 6.4 g of product; MS: (+) m/z 219.4 (M+1)

Workup

  1. temperatureat reflux temperature for 48 hours
  2. filtrationfiltered through a small pad of celite
  3. washthe solid was washed with additional dichloromethane and NaOH solution
  4. customThe biphasic mixture was separated
  5. washthe organic fraction was successively washed with 2 N NaOH and brine
  6. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated to a residue
  8. customThe crude product was purified by column chromatography
  9. washeluting the desired product from silica gel with a gradient of 5-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-39407716486344da8d85cf26567b86b1
Source dataset
uspto-grants-2014_04
Patent number
US08703795B2

Reaction notes

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