Ethyl iodoacetate → Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate

Participants

Reaction Steps

To a solution of 2-(3,4-dichlorophenyl)pent-4-enoyl chloride (2.51 g, 9.53 mmol) and 3-morpholin-4-yl-3-thioxopropanenitrile (1.62 g, 9.53 mmol) in acetonitrile (40.0 mL) in a 100 mL round bottom flask was added N,N-diisopropylethylamine (1.82 mL, 10.5 mmol), and the resulting deep orange/red solution was stirred at room temp for 1 hr. To the resulting mixture was added N,N-diisopropylethylamine (4.15 mL, 23.8 mmol) and then ethyl iodoacetate (1.24 mL, 10.5 mmol). The flask was fitted with a reflux condenser and the reaction was heated to reflux over 48 hrs. The mixture was concentrated and distributed between NaHCO3(aq) saturated solution and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined org layer was washed with brine, dried, and concentrated to provide a dark syrup. Purification on a silica gel column (gradient elution 3-30% EtOAc/hexanes) provided ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate (704 mg, 15.9% yield). LCMS: (AA) ES+ 465, 467, 469; 1H NMR (400 MHz, CDCl3) δ 7.49-7.42 (m, 1H), 7.41-7.33 (m, 1H), 7.31-7.27 (m, 1H), 5.82-5.66 (ddt, J=17.2, 10.1, 6.8 Hz, 1H), 5.62-5.50 (t, J=8.2 Hz, 1H), 5.16-5.08 (dd, J=17.1, 1.6 Hz, 1H), 5.04-4.94 (dd, J=10.2, 1.5 Hz, 1H), 4.35-4.27 (q, J=7.1 Hz, 2H), 3.86-3.78 (m, 4H), 3.59-3.48 (m, 4H), 3.10-2.99 (h, J=6.9 Hz, 2H), 1.40-1.31 (m, 3H).

Provenance & Evidence