2,6-Lutidine → Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-oxopropyl]-5-(morpholin-4-yl)thiophene-2-carboxylate

Participants

Reaction Steps

To a suspension of ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate (247 mg, 0.531 mmol) in 1,4-dioxane (6.00 mL) and water (2.00 mL) was added sodium metaperiodate (454 mg, 2.12 mmol), 2,6-lutidine (246 uL, 2.12 mmol), and 4% osmium tetroxide in water (4:96, osmium tetraoxide:water, 64.9 uL, 0.0106 mmol). The reaction was vigorously stirred at rt for 5 hrs. The mixture was filtered over a celite pad and the filtered solid was rinsed with EtOAc. The filtrate was washed with NaHCO3(aq) saturated solution and the aqueous layer was extracted with EtOAc (×2). The combined organic layer was washed with 1N HCl soln and brine, dried, and concentrated. Purification on a silica gel column (gradient elution 5-50% EtOAc/hexanes) provided ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-oxopropyl]-5-(morpholin-4-yl)thiophene-2-carboxylate as a yellow syrup (108 mg, 43.5% yield). 1H NMR (400 MHz, CDCl3) δ 9.84-9.73 (d, J=1.3 Hz, 1H), 7.48-7.42 (d, J=2.1 Hz, 1H), 7.42-7.32 (d, J=8.4 Hz, 1H), 7.30-7.18 (m, 1H), 6.06-5.94 (t, J=7.7 Hz, 1H), 4.38-4.26 (q, J=7.1 Hz, 2H), 3.86-3.77 (t, J=4.9 Hz, 4H), 3.62-3.51 (dd, J=5.7, 4.0 Hz, 4H), 3.50-3.42 (m, 2H), 1.41-1.29 (m, 3H).

Provenance & Evidence