Cesium carbonate → 4-({[5-Chloro-6-(2,2,2-trifluoro-1,1-dimethylethoxy)pyridin-3-yl]oxy}methyl)-2,5-difluoro-N-(methylsulfonyl)benzamide

HRID 512026

Reaktionsgleichung

Reaktionsgleichung von HRID 512026
[Cl:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:23]([F:24])=[CH:22][C:14]([C:15]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[O:16])=[C:13]([F:25])[CH:12]=2)[CH:5]=[N:6][C:7]=1F.[F:26][C:27]([F:33])([F:32])[C:28]([CH3:31])([OH:30])[CH3:29].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:23]([F:24])=[CH:22][C:14]([C:15]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[O:16])=[C:13]([F:25])[CH:12]=2)[CH:5]=[N:6][C:7]=1[O:30][C:28]([CH3:31])([CH3:29])[C:27]([F:33])([F:32])[F:26]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 681821,1,1-Trifluoro-2-methylpropan-2-ol2×HCID 566445724-{[(5-chloro-6-fluoropyridin-3-yl)oxy]methyl}-2,5-difluoro-N-(methylsulfonyl)benzamide

Produkt 1

HCID 566443644-({[5-Chloro-6-(2,2,2-trifluoro-1,1-dimethylethoxy)pyridin-3-yl]oxy}methyl)-2,5-difluoro-N-(methylsulfonyl)benzamideAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 4-{[(5-chloro-6-fluoropyridin-3-yl)oxy]methyl}-2,5-difluoro-N-(methylsulfonyl)benzamide (Example 23, 0.092 g, 0.233 mmol) in DMSO (1.0 mL) were added 1,1,1-trifluoro-2-methylpropan-2-ol (0.120 g, 0.937 mmol) and caesium carbonate (0.305 g, 0.936 mmol). The mixture was stirred at 100° C. in a pressure vial for 16 hours. Then 1,1,1-trifluoro-2-methylpropan-2-ol (0.120 g, 0.937 mmol) was added to the mixture and heated at 125° C. for another 24 hours. The reaction mixture was diluted with EtOAc (15.0 mL), washed with water (10.0 mL), aqueous citric solution (10%, 10.0 mL) and water (2×10.0 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was suspended in a mixture of heptane and acetone (8:2, 5.0 mL) and sonicated for 2 minutes. The mixture was filtered to yield the title compound as an off-white solid (0.023 g, 20%).

Aufarbeitung

  1. temperatureheated at 125° C. for another 24 hours
  2. washwashed with water (10.0 mL), aqueous citric solution (10%, 10.0 mL) and water (2×10.0 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionThe resulting residue was suspended in a mixture of heptane and acetone (8:2, 5.0 mL)
  7. customsonicated for 2 minutes
  8. filtrationThe mixture was filtered

Quellen und Nachweise

ORD-Eintrag
ord-dded83e9d2074044a8dfacd44ae61164
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102621B2

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