Sodium Azide → (4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-amine

Temperature

80 °C

To a stirred solution of (4aR,7S,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl methanesulfonate (109 mg, 0.347 mmol) under nitrogen in anhydrous DMF (2.0 mL) was added sodium azide (90 mg, 1.387 mmol). The mixture was heated to 80° C. After 24 hours, the mixture was concentrated under reduced pressure. The resultant oil was chromatographed using a Biotage™ 10 g silica gel cartridge eluted with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes. The product fractions were combined and concentrated under reduced pressure. The resultant white solid (67 mg, 0.256 mmol) was dissolved in anhydrous THF (2.0 mL) under nitrogen and a IM solution of trimethylphosphine (0.51 mL, 0.51 mmol) was added. The mixture was allowed to stir at room temperature for 40 minutes until the azide was consumed, then saturated aqueous ammonium hydroxide (0.5 mL) was added. After stirring for 30 minutes, the mixture was concentrated under reduced pressure and dried under high vacuum. The resultant residue was dissolved in acetonitrile (2 mL), frozen at −78° C., and lyophilized to dryness to provide the title compound as a white solid. LC-MS: calculated for C13H17NO3 235.12, observed m/e: 236.19 (M+H)+ (Rt 0.45/4 min).

1. concentrationthe mixture was concentrated under reduced pressure
2. customThe resultant oil was chromatographed
3. washeluted with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes
4. concentrationconcentrated under reduced pressure
5. customwas consumed
6. additionsaturated aqueous ammonium hydroxide (0.5 mL) was added
7. concentrationthe mixture was concentrated under reduced pressure
8. customdried under high vacuum
9. dissolutionThe resultant residue was dissolved in acetonitrile (2 mL)
10. temperaturefrozen at −78° C.

ORD record

ord-5efecd7da7ff441fbf13123b2d250a38

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382243B2