Ethyl cyanoacetate → trans-1-[2-(4-Fluorophenyl)ethyl]-4-methyl-2,6-dioxopiperidine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl cyanoacetate (4.26 mL, 40 mmol) and trans-2-butenoic acid [2-(4-fluoro-phenyl)ethyl]amide (4.15 g, 20 mmol) in tert-butanol (60 mL) was treated with a solution of potassium tert-butoxide in tetrahydrofuran (1.0 M, 40 mL, 40 mmol) and the mixture was heated at 80° C. The mixture was cooled to room temperature after 16.5 hours and diluted with 1.0 N aqueous hydrochloric acid. The mixture was concentrated under vacuum to remove the organic solvents, providing a suspension of solid in the aqueous residue. This was collected by filtration, dried, and purified by recrystallization from 95% ethanol to provide a white solid (5.13 g, 93%). 1H NMR (300 MHz, CDCl3) δ7.19 (m, 2H), 7.00 (t, J=9 Hz, 2H), 4.02 (m, 2H), 3.41 (d, J=11 Hz, 1H), 2.91 (m, 1H), 2.83 (t, J=8 Hz, 2H), 2.5-2.3 (m, 2H), 1.31 (d, J=6 Hz, 3H). Mass spec (CI) m/z 275.0 (M+H+, 100%).

Provenance & Evidence