Cesium fluoride → 1,1,1-trifluoro-3-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-3-phenylpropane-2,2-diol

HRID 13185

Reaction equation

HRID 13185 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH:18]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:19]([O:21]C)=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C[Si](C)(C)[C:31]([F:34])([F:33])[F:32].[F-].[Cs+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.O>[F:32][C:31]([F:34])([F:33])[C:19]([OH:20])([OH:21])[CH:18]([O:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[N:9]=[CH:10]2)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 59339649methyl 2-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-2-phenylacetate

Product 1

HCID 593397361,1,1-trifluoro-3-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-3-phenylpropane-2,2-diolYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl 2-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-2-phenylacetate (147d, 2.5 g, 6.6 mmol) was dissolved in THF (15 mL, dried over 4 Å MS) under Argon atmosphere and cooled in an ice-bath. Trimethyl(trifluoromethyl)silane (1.18 mL, 8 mmol) was added followed by Caesium fluoride (100 mg, 0.66 mmol). The cooling bath was removed and the stirring was continued at r.t. for 4 h. A solution of tetrabutylammonium fluoride in THF (1M, 7 mL, 7 mmol) followed by water (4 mL) was then added and the mixture was stirred for additional 1 h and then partitioned between ethyl acetate and water. The organic phase was washed twice with water, then brine and evaporated to afford 1,1,1-trifluoro-3-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-3-phenylpropane-2,2-diol (2.74 g, 95%)

Workup

  1. temperaturecooled in an ice-bath
  2. customThe cooling bath was removed
  3. additionwas then added
  4. custompartitioned between ethyl acetate and water
  5. washThe organic phase was washed twice with water
  6. custombrine and evaporated

Sources & evidence

ORD record
ord-f9ae0f6d3dd046ca8cdda5139a80df1d
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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