Ammonium Chloride → (4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxine-7-thiol

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Reaction Conditions

Reaction Steps

To a stirred solution of (4aR,7S,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl methanesulfonate (110 mg, 0.350 mmol) under nitrogen in anhydrous DMF (2.0 mL) was added potassium thioacetate (180 mg, 1.575 mmol). The mixture was degassed by pulling a vacuum and introducing nitrogen (3×). The mixture was heated at 80° C. for 5.5 hours. Upon cooling to room temperature, the mixture was diluted with diethyl ether (30 mL), and then washed with brine (20 mL). The aqueous layer was extracted again with diethyl ether (30 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 20 g (2×10 g in series) silica gel cartridge by eluting with 0-30% EtOAc in 1:1 Hexane/DCM over 20 column volumes. The product fractions were combined and concentrated under reduced pressure. The resultant white solid (58 mg, 0.197 mmol) was dissolved in anhydrous methanol (2.0 mL) under nitrogen. In a separate vessel, metallic sodium (9 mg, 0.39 mmol) was dissolved in anhydrous methanol (1.0 mL), then added to the reaction mixture containing the thioester. After stirring for 30 minutes at room temperature, the mixture was poured into saturated aqueous ammonium chloride (30 mL). The mixture was extracted with DCM (50 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to provide the title compound as an off-white solid. LC-MS: calculated for C13H16O3S 252.08, observed m/e: 253.11 (M+H)+ (Rt 1.82/4 min).

Provenance & Evidence