Reaction Steps
A mixture of the above material (0.67 g, 2.0 mmol) and thio-CDI (90% tech, 1.6 g, 8.0 mmol) in anhydrous DMF (20 mL) was stirred at 95° C. overnight. After cooling the solvent was removed under reduced pressure, and the residue was purified on silica gel by flash column chromatography (MeOH/DCM, 1:100 to 5:100), affording a mixture containing O-(-(3aR,4aR,8aS,9R,9aR)-2-(dimethylamino)-7-phenyl-3a,4a,5,8a,9,9a-hexahydro-[1,3]dioxino[4′,5′:5,6]pyrano[3,2-d]thiazol-9-yl) 1H-imidazole-1-carbothioate. This mixture was dissolved in anhydrous THF (30 mL), and Bu3SnH (1.0 g, 3.4 mmol) and ABCN (0.060 mg, 0.24 mmol) was added, and the mixture was stirred at reflux overnight. The solvent was then removed under reduced pressure, and the residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH:DCM, 3:100), affording an pale yellow solid containing -(3aR,4aR,8aS,9aR)-N,N-dimethyl-7-phenyl-3a,4a,5,8a,9,9a-hexahydro-[1,3]dioxino[4′,5′:5,6]pyrano[3,2-d]thiazol-2-amine (0.17 g, impure). The solid was treated with 2% HCl in MeOH (10 mL) at room temperature for 2 h, and then the solvent was removed under reduced pressure. The residue was neutralized with 1.0 M NH3 in MeOH, and subsequently purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH:DCM, 1:10), affording pure -(3aR,5R,6S,7aR)-5-(hydroxymethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-6-ol as an off-white solid (0.050 g, 11% overall yield). 1H NMR (400 MHz, CD3OD) δ 6.23 (d, J=6.4 Hz, 1H), 4.28-4.24 (m, 1H), 3.74 (dd, J=2.5, 12.0 Hz, 1H), 3.70-3.65 (m, 1H), 3.59 (dd, J=6.2, 12.0 Hz, 1H), 3.53-3.48 (m, 1H), 2.99 (s, 6H), 2.14-2.08 (m, 1H), 2.02-1.95 (m, 1H); 13C NMR (100 MHz, CD3OD) δ 165.60, 92.43, 77.19, 69.67, 65.79, 63.27, 40.15, 34.93; MS, m/z=255 (M+23).
