Reaction Steps
(3S,4R,5S,6S)-6-(3-(4-(benzyloxy)benzyl)-4-methylphenyl)tetrahydro-2H-pyran-2,3,4,5-tetrayl tetraacetate (36, 5.29 g, 8.8 mmol) was hydrogenated over 10% Pd/C (50% wet) (0.93 g, 0.44 mmol) in THF (44 mL) under hydrogen at atmospheric pressure for 1 hour. The reaction was filtered through celite, concentrated under vacuum, azeotroped twice with toluene, and placed on the high vacuum to dry thoroughly. The resulting phenol was carried to the next step without further purification. It was combined with thiourea (2.01 g, 26 mmol) and dissolved in dioxane (44 mL). TMSOTf (4.8 mL, 26 mmol) was added. The reaction was heated at 80° C. for 3 hours and then cooled to room temperature. Methyl iodide (2.2 mL, 35 mmol) was added, followed by DIPEA (12 mL, 70 mmol). The reaction was stirred overnight, then quenched with saturated aqueous NaHSO4 (150 mL), stirred vigorously for 2 hours, diluted with EtOAc, washed with H2O and brine (with back extraction), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (gradient 0-50% EtOAc/hexanes) to give 3.88 g (88% yield) of the product 37 as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.10-7.19 (m, 2H), 7.03 (s, 1 H), 6.94 (d, J=8.6 Hz, 2 H), 6.68-6.77 (m, 2 H), 5.33 (t, J=9.3 Hz, 1 H), 5.21 (t, J=9.6 Hz, 1 H), 5.12 (t, J=9.6 Hz, 1H), 4.59 (s, 1 H), 4.52 (d, J=9.9 Hz, 1 H), 4.38 (d, J=9.9 Hz, 1H), 3.82-3.96 (m, 2 H), 2.21 (s, 3 H), 2.18 (s, 3 H), 2.10 (s, 3 H), 2.01 (s, 3 H), 1.75 (s, 3 H); MS (ES+) [M+NH4]+=520.
