反应详情

温度

70 °C

1,2,4-Triazole (274 mg; 3.89 mmol) is dissolved in DMSO (3 ml). Sodium hydride (124 mg; 60% suspension in paraffin; 3.24 mmol) is added and the reaction mixture is heated to 70° C. for one hour. The reaction mixture is cooled to room temperature and 1(S)-[2(S)-(2,5-Difluoro-phenyl)oxiranyl]-ethanol (275 mg; 1.3 mmol) dissolved in DMSO (2 ml) is added slowly over a period of 10 minutes. The reaction mixture is then heated to 70° C. for three hours. The solvent is evaporated. The residue is taken-up in ethyl acetate (10 ml) and water (5 ml). The phases are separated. The aqueous layer is extracted 3 times with ethyl acetate (3 times 5 ml). The combined organic phases are washed twice with water (2 times 5 ml). The organic phase is dried over sodium sulfate. The solids are filtered off and the solvent is removed under reduced pressure. The crude product is dissolved in ethyl acetate (16 ml). Oxalic acid (164 mg; 1.3 mmol) is added and the solution is stirred for 30 minutes. The mixture is stored at 0° C. overnight. The crystalline (2R, 3R)-2-(2,5-Difluoro-phenyl)-1-[1,2,4]triazol-1-yl-butane-2,3-diol oxalate salt is filtered off. The crystals are washed with hexanes and dried under vacuum. The desired compound is obtained as a white powder (337 mg); yield 66.7% with an optical purity higher than 95% (no other isomer is visible in NMR).

1. temperatureThe reaction mixture is cooled to room temperature
2. additionis added slowly over a period of 10 minutes
3. temperatureThe reaction mixture is then heated to 70° C. for three hours
4. customThe solvent is evaporated
5. customThe phases are separated
6. extractionThe aqueous layer is extracted 3 times with ethyl acetate (3 times 5 ml)
7. washThe combined organic phases are washed twice with water (2 times 5 ml)
8. dry with materialThe organic phase is dried over sodium sulfate
9. filtrationThe solids are filtered off
10. customthe solvent is removed under reduced pressure
11. dissolutionThe crude product is dissolved in ethyl acetate (16 ml)
12. waitThe mixture is stored at 0° C. overnight
13. filtrationThe crystalline (2R, 3R)-2-(2,5-Difluoro-phenyl)-1-[1,2,4]triazol-1-yl-butane-2,3-diol oxalate salt is filtered off
14. washThe crystals are washed with hexanes
15. customdried under vacuum