2,6-Lutidine → HCID 59252700, compound

Participants

Reaction Steps

To a solution of 1-benzyl-4-[(3-fluorophenyl)amino]piperidine-4-carbonitrile (Intermediate 1A.1-1, 9.0 g, 29.1 mmol) in dichloromethane (150 ml) were added ethyl malonyl chloride (4.9 ml, 37.8 mmol) and 2,6-lutidine (5.1 ml, 43.6 mmol). The reaction was allowed to stir at rt for 2.5 h. Additional ethyl malonyl chloride (1.1 ml, 8.7 mmol) was added, and the reaction was allowed to stir for 30 min. The reaction was diluted with dichloromethane and washed with water and brine. The organic portion was dried over sodium sulfate, filtered, and concentrated in vacuo to yield a 1:1 mixture of desired ester ethyl 3-[(1-benzyl-4-cyanopiperidin-4-yl)(3-fluorophenyl)amino]-3-oxopropanoate and its acid 3-[(1-benzyl-4-cyanopiperidin-4-yl)(3-fluorophenyl)amino]-3-oxopropanoic acid (quant).

Provenance & Evidence