Reaction #41463

Reaction equation

tetrabutylammonium fluoride

Trimethyl(trifluoromethyl)silane

Methyl 2-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-2-phenylacetate

Caesium fluoride

→

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

Yield 96.0%

Solvents

THF

water

THF

Conditions

Workup

1. 1
   Temperaturecooled in an ice-bath
2. 2
   OtherThe cooling bath was removed
3. 3
   workup.ADDITIONwas then added
4. 4
   Otherpartitioned between ethyl acetate and water
5. 5
   WashThe organic phase was washed twice with water
6. 6
   Otherbrine and evaporated

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%)

Source