Sodium Iodide → Ethyl 2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-3-carboxylate 1,1-dioxide

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Reaction Steps

A solution of potassium t-butoxide in t-butanol (1M, 15.7 mL, 15.7 mmol) was added to a solution of the product of Step A (4.80 g, 14.95 mmol) in anhydrous DMF (50 mL) at 0° C. followed by 1-bromo-3-methoxypropane (3.43 g, 22.4 mmol) and sodium iodide (0.2 g). The mixture was stirred for 5 h at ambient temperature, poured into ice water (300 mL) and extracted with ethyl acetate (2×200 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a viscous liquid which was dissolved in acetone (300 mL); p-toluenesulfonic acid (0.4 g) was added and this mixture was heated at reflux temperature for 4.5 h. A saturated aqueous solution of sodium bicarbonate (100 mL) was added to the reaction mixture and acetone was evaporated. The aqueous mixture was extracted with ethyl acetate (2×200 mL) and the combined extracts were dried (MgSO4), filtered and evaporated to give crude aldehyde which was dissolved in ethyl acetate (100 mL). DBN (0.2 g) was added and the mixture heated at reflux temperature for 2 h under nitrogen. The mixture was cooled, quenched with a 2N HCl (50 mL) and extracted with ethyl acetate (2×150 mL). The combined extracts were dried (MgSO4) and evaporated to a syrup which was purified by column chromatography (silica, 30% ethyl acetate/hexane) to give a white solid (2.68 g, 54%): mp 82°-83° C.

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