Nitrogen → HCID 58171476, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate (196 mg, 0.667 mmol), copper iodide (39 mg, 0.3 equiv) and dry THF (4 mL) was degassed and recharged with N2 gas (3×), and cooled to 0° C. A solution of o-tolylmagnesium bromide (2.0 M in ether, 600 μL, 1.8 equiv) was added dropwise. The mixture was stirred 1 h at 0° C. under protection of N2 gas before being warmed to rt slowly and stirred 2 h at rt. LC-MS found the reaction was complete. The mixture was cooled to 0° C. again, quenched with 2% aq HCl to pH=˜5, extracted with EtOAc (3×35 mL). The combined organic layers were washed with satd NH4Cl (10 mL) and brine (10 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 12-g silica gel cartridge, eluted with a 0 to 30% EtOAc in hexanes gradient, to afford tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-o-tolylpiperidine-1-carboxylate (226 mg, 88%) as a clear oil.

Provenance & Evidence