反应详情

温度

55 °C

To a mixture of tert-butyl 5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-ylcarbamate (0.64 g, 1.89 mmol) in THF (6 mL) was added cesium carbonate (1.07 g, 3.28 mmol). The mixture was heated to 55° C. for 10 minutes and then tert-butyl (4R)-4-((S)-((tert-butyl(dimethyl)silyl)oxy)(4-(trifluoromethyl)phenyl)methyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (0.84 g, 1.64 mmol) in THF (4 mL) was added. The mixture was heated for 1 hour after the addition. HPLC-MS showed the product and thiadiazole starting material. The reaction was concentrated in vacuo and EtOAc (75 mL) was added. The mixture was cooled to 0° C. and 5% HCl (50 mL) was slowly added. The mixture was stirred for 1 hour. The organic phase was separated, and the aqueous phase was extracted twice with EtOAc. To the combined EtOAc solution was added saturated NaHCO3 and Na2CO3 until it was basic (pH=9). The organic layer was washed with brine, dried over Na2SO4, and then concentrated in vacuo. The residue was purified by chromatography on silica gel (50%-100% DCM-hexane) to provide the product as a yellow solid (1.18 g, 93%). LCMS (API-ES) m/z: 772 (M+H+).

1. temperatureThe mixture was heated for 1 hour
2. additionafter the addition
3. concentrationThe reaction was concentrated in vacuo and EtOAc (75 mL)
4. additionwas added
5. temperatureThe mixture was cooled to 0° C.
6. addition5% HCl (50 mL) was slowly added
7. customThe organic phase was separated
8. extractionthe aqueous phase was extracted twice with EtOAc
9. additionTo the combined EtOAc solution was added saturated NaHCO3 and Na2CO3 until it
10. washThe organic layer was washed with brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated in vacuo
13. customThe residue was purified by chromatography on silica gel (50%-100% DCM-hexane)