Benzyl 3-O-Benzyl-4,6-O-benzylidene-a-D-mannopyranoside synthesis

Yield:62774-16-7 115 g

Reaction Conditions:

Stage #1: (4aR,6S,7S,8R,8aS)-6-benzyloxy-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[5,6-d][1,3]dioxine-7,8-diolwith di(n-butyl)tin oxide in toluene at 120; for 3 h;
Stage #2: benzyl bromidewith tetrabutylammomium bromide;cesium fluoride in toluene at 120; for 3 h;

Steps:

3 (4aR,6S,7S,8R,8aS)-6-Benzyloxy-8-methyl-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2- d][1,3]dioxin-7-ol

Step 3; To a suspension of (4aR,6S,7S,8R,8aS)-6-benzyloxy-2-phenyl-4,4a,6,7,8,8a- hexahydropyrano[3,2-d][1,3]dioxine-7,8-diol (114.3 g, 319 mmol) in dry toluene (1000 mL) was added Bu₂SnO (81 g, 325 mmol). The reaction mixture was stirred for 3 h at 120 ^oC. It was then allowed to cool to ambient temperature. Bu4NBr (109 g, 338 mmol), cesium fluoride (49.4 g, 325 mmol), and benzyl bromide (39.8 mL, 335 mmol) were added. The reaction mixture was stirred for 3 h at 120 ^oC, then allowed to cool to ambient temperature and diluted with ethyl acetate. The organic phase was washed with saturated NaHCO₃, and then filtered over Celite. The water phase was extracted with ethyl acetate. The combined organic phase was washed again with water, dried, and concentrated. The crude product was purified by column chromatography (hexanes to hexanes/ethyl acetate 1:1) to give (4aR,6S,7S,8R,8aS)-6-benzyloxy-8-methyl-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2- d][1,3]dioxin-7-ol (115 g).¹H NMR (400 MHz, CD3OD): δ 7.18-7.54 (m, 15H), 5.59 (s, 1H), 4.86 (s, 1H), 4.58-4.70 (m, 3H), 4.49 (d, 1H), 4.02-4.20 (m, 3H), 3.74-3.90 (m, 3H) ppm (protons on NH and OH were not visible).

References:

WO2018/9539,2018,A1 Location in patent:Page/Page column 78; 79