Reaction #1005949

Reaction equation

2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-4-(trifluoro-methyl)pyrimidine-5-carboxylic acid

thionyl chloride

→

title compound

Yield 86.0%

{2-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-pyrimidin-5-yl}methanol

Yield 86.0%

Solvents

1,2-dichloroethane

Conditions

Workup

1. 1
   Temperaturethe mixture was refluxed
2. 2
   Temperatureunder heating for 5 hours
3. 3
   OtherAfter removing the solvent
4. 4
   Otherby evaporation
5. 5
   workup.DISSOLUTIONthe residues were dissolved in 1,4-dioxane (20 mL)
6. 6
   workup.ADDITIONthe resulting solution was added dropwise to the mixture solution comprising water (30 mL), 1,4-dioxane (30 mL), and sodium borohydride (0.4 g) under ice cooling
7. 7
   workup.ADDITIONAfter the dropwise addition
8. 8
   Temperaturethe solution was refluxed
9. 9
   Temperatureunder heating for one hour
10. 10
    TemperatureAfter cooling
11. 11
    workup.ADDITIONthe reaction solution was poured over ice water
12. 12
    Extractionextracted with ethyl acetate
13. 13
    TemperatureAfter cooling
14. 14
    Extractionthe extraction
15. 15
    workup.ADDITIONby adding water and ethyl acetate to the solution
16. 16
    DryingThe organic layer was dried over magnesium sulfate
17. 17
    OtherThe solvent was evaporated off under reduced pressure
18. 18
    Otherthe residue was then purified by a silica gel chromatography

Procedure

2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-4-(trifluoro-methyl)pyrimidine-5-carboxylic acid (2.0 g) was added to 1,2-dichloroethane (50 mL). To the resulting mixture, thionyl chloride (1.0 g), and one drop of N,N-dimethylformamide was added and the mixture was refluxed under heating for 5 hours. After removing the solvent by evaporation, the residues were dissolved in 1,4-dioxane (20 mL), and the resulting solution was added dropwise to the mixture solution comprising water (30 mL), 1,4-dioxane (30 mL), and sodium borohydride (0.4 g) under ice cooling. After the dropwise addition was completed, the solution was refluxed under heating for one hour. After cooling, the reaction solution was poured over ice water and then extracted with ethyl acetate. After cooling, the extraction was carried out by adding water and ethyl acetate to the solution. The organic layer was dried over magnesium sulfate. The solvent was evaporated off under reduced pressure, and the residue was then purified by a silica gel chromatography to obtain the title compound (1.65 g, 86%).

Source