Acetic Acid → TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATE

Participants

Reaction Conditions

Reaction Steps

Ethyl cyanoacetate (3.475 mL, 1.3 equiv), ammonium acetate (1.16 g, 0.6 equiv), acetic acid (1.725 mL, 1.2 equiv) were added to a solution of N-Boc-4-piperidone (5 g, 25.11 mmol) in toluene (55 mL). The mixture was heated at 110° C. for 2 h, 85° C. overnight, then at 135° C. for 4 h. The mixture was washed with 5% aq NaOH (15 mL), water (15 mL) and brine (10 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 120-g silica gel cartridge, eluted with a 5 to 40% EtOAc in hexanes gradient, to afford tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate (4.71 g, 64%) as an off-white solid.

Provenance & Evidence