Ethyl Acetate → ethyl 3-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)benzoate

HRID 20571Notes

Reaction equation

HRID 20571 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].[CH2:28]([O:30][C:31](=[O:40])[C:32]1[CH:37]=[CH:36][C:35](F)=[C:34]([F:39])[CH:33]=1)[CH3:29].C(OCC)(=O)C>CC(N(C)C)=O>[F:39][C:34]1[CH:33]=[C:32]([CH:37]=[CH:36][C:35]=1[O:7][C:8]1[CH:9]=[C:10]([C:11]([NH:13][C:14]2[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=2)=[O:12])[CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:31]([O:30][CH2:28][CH3:29])=[O:40]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2737171Ethyl 3,4-difluorobenzoateHCID 593468923-Hydroxy-5-{[(S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 59346875ethyl 3-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)benzoateYield 31%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

Cesium carbonate (8.3 g, 25.4 mmol) was added to a mixture of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (3.7 g, 12.7 mmol) and ethyl-3,4-difluorobenzoate (2.36 g, 12.7 mmol) in dimethylacetamide (60 mL) and the stirred mixture heated at 115° C. for 3 hours. The mixture was allowed to cool to RT and ethyl acetate (100 mL) added. The mixture was washed with water (5×40 mL), brine (40 mL), dried (MgSO4), filtered, and reduced in vacuo. The residue was chromatographed on silica, eluting with 50% ethyl acetate in isohexane, to give the desired compound (1.8 g).

Workup

  1. temperatureto cool to RT
  2. washThe mixture was washed with water (5×40 mL), brine (40 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customThe residue was chromatographed on silica
  6. washeluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-f85d8d4314614d2894d6f7d6e5575885
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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