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

HRID 1848792노트

반응식

HRID 1848792 반응식
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

참가 물질

8

반응물 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

생성물 1

HCID 86706791[6-({2',6'-Dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acid수율 53.2%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 80711,2-Dimethoxyethane용매

실험 절차

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%.

후처리

  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

출처 및 근거

ORD 기록
ord-4ea9d12aa4124a2695f1e8f08979f35b
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952185B2

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