methyl 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranoside

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The crude methyl 2,3,4,6-tetra-O-benzyl-D-glucopyranoside 10 (210 g) is dissolved in glacial acetic acid (500 mL) and the solution is heated to nearly boiling. Hot sulfuric acid solution (3N, 130 mL) is added slowly. Heat is periodically increased and more acetic acid (20 mL) is added to dissolve any precipitate. The final cloudy solution is heated at 100°-110° C. for 2 h. After cooling, crude crystalline product is isolated by filtration and washed several times with methanol to yield product 11 as white crystals (109 g, 53%): mp. 168°-170° C. (Lit. 169°-171° C.). the solution is heated Heat is periodically increased to dissolve any precipitate The final cloudy solution is heated at 100°-110° C. for 2 h After cooling crude crystalline product is isolated by filtration washed several times with methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl-α-D-glucopyranoside 9 (75 g) is dissolved in benzyl chloride (400 mL). To this solution is added potassium hydroxide (250 g). The resulting suspension is heated at 100° C. (water bath temp.) with stirring (mechanical) for 4 h, then cooled to r.t. The mixture is washed with saturated NaCl in ether (500 mL) and dried with MgSO4. The ether is evaporated. The residue is distilled under vacuum (~0.1 mm Hg) at a temperature of 120° C. until no more distillate is collected or the temperature at the distilling head begins to fall. The pot residue is used for the next reaction without further purification. The mixture is washed with saturated NaCl in ether (500 mL) dried with MgSO4 The ether is evaporated The residue is distilled under vacuum (~0.1 mm Hg) at a temperature of 120° C. until no more distillate is collected The pot residue is used for the next reaction without further purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Preparation of 2,3,4,6-Tetra-O-benzyl-α-D-glucopyranose Methyl-α-D-glucopyranose (100 g, 0.516 mol) is suspended in benzyl chloride (400 mL, 3.5 mol) with KOH pellets (336 g, 6 mol), and the mixture is stirred using a mechanical stirrer at 120°-130° C. for 3 h. The reaction mixture is cooled and water (800 mL) is added to dissolve the crystalline mass, which is extracted with ether (2×200 mL). The combined organic layer is washed with water (2×500 mL) and dried (Na2SO4). The solvents are removed by vacuum distillationto give the crude methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside for the next reaction. at 120°-130° C. for 3 h The reaction mixture is cooled to dissolve the crystalline mass, which is extracted with ether (2×200 mL) The combined organic layer is washed with water (2×500 mL) dried (Na2SO4) The solvents are removed by vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of NaH (5.19 g of a 60% dispersion in oil, 130 mmol) in DMF (150 mL) was added portionwise methyl-α-D-glucopyranoside (4.2 g, 21.6 mmol). The resulting mixture was stirred at rt for 2 hr, to which tetrabutyl ammonium bromide (800 mg, 2.16 mmol) was and followed by dropwise addition of benzyl bromide (11.58 mL, 97 mmol). After stirring at rt overnight, the mixture was concentrated and the residue was suspended in water and extracted with ether (3×150 mL). The combined ether layers were washed with brine (200 mL), dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography on silica gel (330 g), eluting with 0-30% EtOAc in hexanes to give the title compound. 1H NMR (CDCl3, 400 MHz) δ 3.44 (s, 3H), 3.62 (dd, J=9.6, 3.5, 1H), 3.66-3.72 (m, 2H), 3.75-3.82 (m, 2H), 4.04 (t, J=9.3, 1H), 4.51-4.55 (m, 2H), 4.66 (d, J=12.1, 1H), 4.69 (d, J=3.5, 1H), 4.72 (d, J=12.1, 1H), 4.83-4.90 (m, 3H), 5.04 (d, J=11.0, 1H), 7.19 (m, 2H), 7.30-7.43 (m, 18H). the mixture was concentrated extracted with ether (3×150 mL) The combined ether layers were washed with brine (200 mL) dried over Na2SO4 filtered evaporated The residue was purified by flash chromatography on silica gel (330 g) eluting with 0-30% EtOAc in hexanes