Diethyl Malonate → Diethyl (5-(5-((tert-butoxycarbonyl)((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)amino)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)propanedioate

Participants

Reaction Steps

To a solution of sodium hydride (60% dispersion in mineral oil, 0.15 g, 3.74 mmol) in dioxane (2 mL) was added a solution of diethyl malonate (0.57 mL, 3.74 mmol) in dioxane (3 mL). The mixture was stirred for 15 minutes and then a solution of 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 (0.58 g, 0.75 mmol) in dioxane (3 mL) was added. The reaction mixture was stirred 16 hours, concentrated in vacuo, and the reaction was quenched with saturated NH4Cl. The mixture was extracted with EtOAc three times. The organic phase was dried over Na2SO4, concentrated in vacuo and purified by chromatography on silica gel (0-15% EtOAc-hexane) to provide the product as a yellow solid (0.68 g, 99%). LCMS (API-ES) m/z: 856 (M+H+-56).

Provenance & Evidence