Diethyl Malonate → HCID 67089220, compound

Participants

Reaction Steps

A 60% dispersion of sodium hydride in mineral oil (48 mg, 1263 μmol) was added to a solution of diethyl malonate (191 μL, 1263 μmol) in THF (2 mL) and the mixture was stirred at room temperature for 15 minutes. This mixture was added to a solution of tert-butyl (R)-4-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)butan-2-ylcarbamate (171 mg, 316 μmol) in THF (3 mL) and the mixture was stirred at room temperature for 4 hours. The mixture was concentrated under reduced pressure, and the residue was partitioned between saturated aqueous NH4Cl (15 mL) and DCM (15 mL). The layers were separated and the aqueous layer was extracted with DCM (2×15 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow solid was dissolved in MeOH/DCM, absorbed onto silica gel, and purified by flash chromatography (silica gel, 40% to 70% EtOAc/hexanes) to provide diethyl 2-(5-(5-((R)-3-(tert-butoxycarbonylamino)-4-(6-(trifluoromethyl)pyridin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)malonate (204 mg, 95% yield) as a yellow solid. LCMS (API-ES) m/z: 703.6 (M+Na+).

Provenance & Evidence