Cesium carbonate → tert-Butyl ((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

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+).

Provenance & Evidence