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

Temperature

80 °C

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).

1. customThe mixture was degassed
2. additionintroducing nitrogen (3×)
3. temperatureUpon cooling to room temperature
4. additionthe mixture was diluted with diethyl ether (30 mL)
5. washwashed with brine (20 mL)
6. extractionThe aqueous layer was extracted again with diethyl ether (30 mL)
7. dry with materialThe combined organic layers were dried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe resultant residue was chromatographed
10. washby eluting with 0-30% EtOAc in 1:1 Hexane/DCM over 20 column volumes
11. concentrationconcentrated under reduced pressure
12. additionadded to the reaction mixture
13. extractionThe mixture was extracted with DCM (50 mL)
14. dry with materialThe organic layer was dried over sodium sulfate
15. concentrationconcentrated under reduced pressure

ORD record

ord-02b7e2d5839145cca79b9efae157bfe4

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382243B2