Thionyl Chloride → {2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-1,3-thiazol-5-yl}methanol

HRID 918772Notes

Reaction equation

HRID 918772 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:27]([F:30])([F:29])[F:28])[CH2:14][CH2:13][N:12]([C:15]3[S:16][C:17]([C:24](O)=[O:25])=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].S(Cl)(Cl)=O>CN(C)C=O.ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:27]([F:30])([F:28])[F:29])[CH2:14][CH2:13][N:12]([C:15]3[S:16][C:17]([CH2:24][OH:25])=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8]

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 594533662-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxylic acid

Product 1

HCID 59453386{2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-1,3-thiazol-5-yl}methanolYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolvent

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%).

Workup

  1. temperaturewas then refluxed
  2. temperatureunder heating for 5 hours
  3. customAfter removing the solvent
  4. customby evaporation
  5. dissolutionthe residues were dissolved in 1,4-dioxane (20 mL)
  6. 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. additionAfter the dropwise addition
  8. temperaturethe reaction solution was refluxed
  9. temperatureunder heating for one hour
  10. temperatureAfter cooling
  11. additionthe reaction solution was poured over ice water
  12. extractionextracted with ethyl acetate
  13. temperatureAfter cooling
  14. extractionthe extraction
  15. additionby adding water and ethyl acetate
  16. dry with materialThe organic layer was dried over magnesium sulfate
  17. customThe solvent was evaporated off under reduced pressure
  18. customthe residue was then purified by a silica gel chromatography

Sources & evidence

ORD record
ord-4bdf0268003d4e3999bbc3904773ed83
Source dataset
uspto-grants-2016_03
Patent number
US09271499B2

Reaction notes

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