Morpholine → 6-Chloro-2-[2-(4-morpholinyl)ethyl]-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxide

Participants

Reaction Steps

To a solution of the product from Step A (0.76 g, 2.20 mmol) in tetrahydrofuran (30 mL) containing triethylamine (0.56 g, 5.5 mmol) was added methanesulfonic anhydride (0.75 g, 4.3 mmol); this mixture was stirred at room temperature for 1 hr and evaporated to dryness. The residue was dissolved in DMF (30 mL), triethylamine (1 mL) was added and the mixture heated at 150° C. for 45 min. Morpholine (3 mL, 34 mmol) was added to the reaction mixture and heating continued at the same temperature for 1 hr followed by heating at 100° C. for an additional hour. The volatiles were evaporated and the residue mixed with ethyl acetate; this mixture was washed with saturated aqueous sodium bicarbonate, dried (MgSO4) and evaporated to an oil which was purified by column chromatography (silica, 50% ethyl acetate/hexane to ethyl acetate) to give a viscous oil (0.42 g, 58%) which was used in the next step.

Provenance & Evidence