Reaction #1005954

Reaction equation

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

Thionyl chloride

→

title compound

Yield 65.0%

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

Yield 65.0%

Solvents

1,2-dichloroethane

Conditions

Workup

1. 1
   Temperaturewas then 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.ADDITIONadded dropwise to the mixture solution comprising water (30 mL), 1,4-dioxane (30 mL), and sodium borohydride (0.5 g) under ice cooling
7. 7
   workup.ADDITIONAfter the dropwise addition
8. 8
   Temperaturethe reaction 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
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)-1,3-thiazole-5-carboxylic acid (2.2 g) was added to 1,2-dichloroethane (50 mL). Thionyl chloride (1.0 g) and one drop of N,N-dimethylformamide were added to the mixture, which was then refluxed under heating for 5 hours. After removing the solvent by evaporation, the residues were dissolved in 1,4-dioxane (20 mL), and then added dropwise to the mixture solution comprising water (30 mL), 1,4-dioxane (30 mL), and sodium borohydride (0.5 g) under ice cooling. After the dropwise addition was completed, the reaction 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 again carried out by adding water and ethyl acetate. 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 (1.1 g, 65%).

Source