反应详情

温度

80 °C

A mixture of (2S,3R)-3-(2,5-Difluoro-phenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-yl-butyronitrile (30.5 g, 0.110 mol), diethyldithiophospate (235 ml) and H2O (110 ml) was stirred at 80° C. for 2 hrs. The reaction mixture was cooled down to r.t. n-Hexane (400 ml) and water (200 ml) was added. The whole was shaken well and the aqueous layer was separated. The remaining organic layer was further extracted with H2O (100 ml×3). All the aqueous layer was combined. Cooled down to 0° C. and neutralized and basified (PH8) with NaHCO3. This basic(PH8) aqueous layer was extracted with EtOAc (300 ml+100 ml×3). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to give dark brown syrup. By addition of CH2Cl2 (100 ml) to this crude syrup, precipitate was formed. The precipitate was filtered and washed with CH2Cl2-hexane (5:1 mixture) to give (2R,3R)-3-(2,5-Difluoro-phenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-ylthiobutyramide (19.2 g, 56%) as white powder. On the other hand, the filtrate was concentrated in vacuo and the residue was chromatographed on silica gel (Wako-gel C-300, CH2Cl2:MeOH=20:1) to give additional (2R,3R)-3-(2,5-Difluoro-phenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-ylthiobutyramide (7.46 g, 22%) as pale brown amorphous powder. Physical form: White solid; FAB-MS: m/z 313 (M+H)+; 1H-NMR (CDCl3): 1.12(3H,d,J=7.3 Hz),3.74(1H,q,J=7.3 Hz), 4.55,5.12 (2H,ABq,J=14.5 Hz), 5.84(1H,s),6.85˜7.02(2H,m),7.15˜7.22(1H,m),7.80 (1H,s),7.89(1H,s), 7.89(1H,brs),8.43(1H,brs).

1. additionwas added
2. stirringThe whole was shaken well
3. customthe aqueous layer was separated
4. extractionThe remaining organic layer was further extracted with H2O (100 ml×3)
5. temperatureCooled down to 0° C.
6. extractionThis basic(PH8) aqueous layer was extracted with EtOAc (300 ml+100 ml×3)
7. dry with materialThe combined organic layer was dried over Na2SO4
8. concentrationconcentrated in vacuo
9. customto give dark brown syrup
10. customprecipitate was formed
11. filtrationThe precipitate was filtered
12. washwashed with CH2Cl2-hexane (5:1 mixture)