Toluene → [6-({2',6'-Dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acid

HRID 1848790Notes

Reaction equation

HRID 1848790 reaction equation
FC(F)(F)S([O:6][C:7]1[CH:20]=[CH:19][C:10]2[C@H:11]([CH2:14][C:15]([O:17]C)=[O:16])[CH2:12][O:13][C:9]=2[CH:8]=1)(=O)=O.[CH3:23][C:24]1[CH:29]=[C:28]([O:30][CH2:31][CH2:32][CH2:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:27]=[C:26]([CH3:38])[C:25]=1[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45]O)[CH:40]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>CN(C)C=O.O>[CH3:38][C:26]1[CH:27]=[C:28]([O:30][CH2:31][CH2:32][CH2:33][S:34]([CH3:37])(=[O:35])=[O:36])[CH:29]=[C:24]([CH3:23])[C:25]=1[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][O:6][C:7]2[CH:20]=[CH:19][C:10]3[C:11]([CH2:14][C:15]([OH:17])=[O:16])=[CH:12][O:13][C:9]=3[CH:8]=2)[CH:40]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 593425562',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)(1,1'-biphenyl)-3-methanolHCID 86667620methyl(S)-2-(6-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 86706791[6-({2',6'-Dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acidYield 65.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl(S)-2-(6-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzofuran-3-yl)acetate (4.88 g) and (2′,6′-dimethyl-4′-(3-(methylsulfonyl)propoxy)-[1,1′-biphenyl]-3-yl)methanol (5.00 g) in N,N-dimethylformamide (15 mL) was added tripotassium phosphate (4.57 g), and the mixture was stirred at 70° C. for 3 hr. The mixture was allowed to cool to room temperature, toluene (60 mL) and water (60 mL) were added, and an extraction operation was performed. The organic layer was washed with water (60 mL) and 10% brine (60 mL), and concentrated. The obtained oil was dissolved in dimethyl sulfoxide (30 mL), and 2N sodium hydroxide (8 mL) was added at room temperature. The mixture was stirred at 70° C. for 1 hr, and allowed to cool to room temperature. Ethyl acetate (60 mL) and water (60 mL) were added, and the mixture was partitioned. The aqueous layer was acidified with 6N hydrochloric acid to pH 1, ethyl acetate (60 mL) was added, and an extraction operation was performed. The organic layer was washed with water (60 mL), and concentrated. The crude product was recrystallized from acetone (30 mL)-water (60 mL), and the obtained solid was dried at 60° C. under reduced pressure to give the title compound (4.91 g) as white crystals. Yield 65%.

Workup

  1. temperatureto cool to room temperature
  2. washThe organic layer was washed with water (60 mL) and 10% brine (60 mL)
  3. concentrationconcentrated
  4. dissolutionThe obtained oil was dissolved in dimethyl sulfoxide (30 mL)
  5. addition2N sodium hydroxide (8 mL) was added at room temperature
  6. stirringThe mixture was stirred at 70° C. for 1 hr
  7. temperatureto cool to room temperature
  8. additionEthyl acetate (60 mL) and water (60 mL) were added
  9. customthe mixture was partitioned
  10. additionwas added
  11. washThe organic layer was washed with water (60 mL)
  12. concentrationconcentrated
  13. customThe crude product was recrystallized from acetone (30 mL)-water (60 mL)
  14. customthe obtained solid was dried at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-ccc3dd49adb34973a3332aaa8585dd90
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

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