反应详情

温度

60 °C

165 mg (0.55 mmol) of (2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-yl-butyric acid were dissolved in 3.3 ml of tetrahydrofuran and, after the addition of 120 mg (0.72 mmol) of 1,1′-carbonyldiimidazole, stirred for 2 hours at 60° C. The reaction mixture was poured onto 10 ml of aqueous 0.5N HCl, extracted twice with each 25 ml of ethyl acetate, dried and evaporated to dryness. The crude residue was dissolved in 6 ml of aqueous 25% ammonium hydroxide and, after the addition of 2 mg of dimethylaminopyridine, stirred at room temperature for 1 hour. After evaporation of the reaction mixture the resulting residue was treated with 200 mg of POCl3 at 40° C. for 3 hours. After evaporation of the excess POCl3 under reduced pressure the crude product was poured onto water and extracted twice with 15 ml of ethyl acetate. The organic phase was dried with Na2SO4 and evaporated. Column chromatography on silica gel (eluent ethyl acetate/n-hexane=1:1) gave 95 mg (74%) of (2R,3R)-3-(2,4-difluorophenyl-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-ylbutyronitrile.

1. extractionextracted twice with each 25 ml of ethyl acetate
2. customdried
3. customevaporated to dryness
4. dissolutionThe crude residue was dissolved in 6 ml of aqueous 25% ammonium hydroxide
5. additionafter the addition of 2 mg of dimethylaminopyridine
6. stirringstirred at room temperature for 1 hour
7. customAfter evaporation of the reaction mixture the resulting residue
8. additionwas treated with 200 mg of POCl3 at 40° C. for 3 hours
9. customAfter evaporation of the excess POCl3 under reduced pressure the crude product
10. additionwas poured onto water
11. extractionextracted twice with 15 ml of ethyl acetate
12. dry with materialThe organic phase was dried with Na2SO4
13. customevaporated