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

HRID 1848792Notes

Reaction equation

HRID 1848792 reaction equation
C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.FC(F)(F)S([O:24][C:25]1[CH:38]=[CH:37][C:28]2[C@H:29]([CH2:32][C:33]([O:35]C)=[O:34])[CH2:30][O:31][C:27]=2[CH:26]=1)(=O)=O.[CH3:41][C:42]1[CH:47]=[C:46]([O:48][CH2:49][CH2:50][CH2:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:45]=[C:44]([CH3:56])[C:43]=1[C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63]O)[CH:58]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:56][C:44]1[CH:45]=[C:46]([O:48][CH2:49][CH2:50][CH2:51][S:52]([CH3:55])(=[O:53])=[O:54])[CH:47]=[C:42]([CH3:41])[C:43]=1[C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63][O:24][C:25]2[CH:38]=[CH:37][C:28]3[C:29]([CH2:32][C:33]([OH:35])=[O:34])=[CH:30][O:31][C:27]=3[CH:26]=2)[CH:58]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 95417Dibenzylidene acetoneHCID 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 53.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of tris(dibenzylideneacetone)dipalladium (0). dibenzylideneacetone solvate (42.5 mg) and 2-(dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl) (76.18 mg) in toluene (4 ml) and 1,2-dimethoxyethane (4 ml) was stirred at 70° C. for 1 hr. After allowing to cool to room temperature, methyl(S)-2-(6-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzofuran-3-yl)acetate (864.3 mg), (2′,6′-dimethyl-4′-(3-(methylsulfonyl)propoxy)-[1,1′-biphenyl]-3-yl)methanol (1.15 g) and cesium carbonate (2.60 g) were added, and the mixture was stirred at 85° C. for 6 hr. The mixture was allowed to cool to room temperature and concentrated, toluene (30 mL) and water (30 mL) were added, and an extraction operation was performed. The organic layer was washed with water (30 mL) and 10% brine (30 mL), and concentrated. The obtained oil was dissolved in dimethyl sulfoxide (15 mL), and 2N sodium hydroxide (4 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 (30 mL) and water (30 mL) were added, and the mixture was partitioned. The aqueous layer was acidified with 6N hydrochloric acid to pH 1, ethyl acetate (30 mL) was added, and an extraction operation was performed. The organic layer was washed with water (30 mL), and concentrated. The crude product was recrystallized from acetone (15 mL)-water (30 mL), and the obtained solid was dried at 60° C. under reduced pressure to give the title compound (706 mg) as white crystals. Yield 53%.

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated
  3. additiontoluene (30 mL) and water (30 mL) were added
  4. washThe organic layer was washed with water (30 mL) and 10% brine (30 mL)
  5. concentrationconcentrated
  6. dissolutionThe obtained oil was dissolved in dimethyl sulfoxide (15 mL)
  7. addition2N sodium hydroxide (4 mL) was added at room temperature
  8. stirringThe mixture was stirred at 70° C. for 1 hr
  9. temperatureto cool to room temperature
  10. additionEthyl acetate (30 mL) and water (30 mL) were added
  11. customthe mixture was partitioned
  12. additionwas added
  13. washThe organic layer was washed with water (30 mL)
  14. concentrationconcentrated
  15. customThe crude product was recrystallized from acetone (15 mL)-water (30 mL)
  16. customthe obtained solid was dried at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-4ea9d12aa4124a2695f1e8f08979f35b
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

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