methyl α-D-glucopyranoside (>99%, Sigma-Aldrich)

Benzyl chloride (99%, Sigma-Aldrich)

Pottasium hydroxide (90%, Sigma-Aldrich)

Dioxane (99+%, Acros)

Sulfuric acid (95.9%, J. T. Baker)

Acetic acid (>99.7, Sigma-Aldrich)

Three neck 1 L RBF equipped with additional funnel, mechanical stirrer and a stopper, was charged with methyl α-D-glucopyranoside (20 g, 0.103 mol, 1 eq.) and dioxane (5 mL per 1 g). The flask was then heated to 80 °C for 0.5 hr. Powdered KOH (99.3 g, 1.17 mol, 17.2 eq.) was added portion wise to the flask (coffee grinder was used to make KOH pellets to very fine powder). After stirring at 1 hr. at the same temperature BnCl (118.6 mL, 1.03 mol, 10.2 eq.) was added to the flask drop wise by using additional funnel. TLC was used to monitor the progress of the reaction. After completion of the reaction (usually over night) water (10mL per 1g) was added to the resulting reaction mixture. The combined solutions were extracted with Ethylacetate (3x 10 mL per 1 g), organic layer was washed with Brine (10 mL per 1 g), dried with Na₂SO₄ and solvents were removed under reduced pressure. The resulting residue was purified by column chromatography by using EtOAc: Hexanes, initially with 10% Ethylacetate in Hexanes to remove the excess benzylchloride, then with 30% Ethylacetate in Hexanes to get 87% yield of tetra-O-benzylmethy α-D-glucopyranoside (50 g, 0.09 mol) as a light clear colorless oil.

Three neck 1L RBF equipped with the condenser and two stoppers was charged sequentially with tetra-O-benzylmethyl α-D-methylglucopyranoside (31 g, 0.055 mol, 1 eq.), AcOH (950 mL) and 2N H₂SO₄ (480 mL). Then the reaction flask was heated to 90- 95 °C, during the course of the reaction white precipitate was recrystallized out of the reaction mixture. TLC was used to analyze the progress of the reaction. After the consumption of the starting material (18 hr.) cold water (1.5 L) was added. The resulting white-solid solution was filtered, Solids were sequentially washed with cold 80% Methanol (300 mL) and Hexanes (300 mL) to get pure 75% yield of tetra-O-benzyl-D-glucopyranose (22.5 g, 0.041 mmol) as a white solid, which could be used for the other reactions without further purification.

¹H NMR (400 MHz, CDCl₃) δ 7.13- 7.31 (m, 34H), 5.21 (d, J= 3Hz, 1H), 4.90- 4.95 (m, 2H), 4.46- 4.84 (m, 12H), 3.95- 4.04 (m, 2H), 3.37- 3.72 (m, 8H), 3.11 (broad s, 2H).

¹³C NMR (100 MHz, CDCl₃) δ 138.8, 138.7, 138.5, 138.4, 138.1, 138.0, 137.9, 128.7, 128.5, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 97.6, 91.4, 84.7, 83.3, 81.9, 80.2, 78.0, 77.9, 75.9, 75.1, 74.9, 73.6, 73.4, 70.4, 69.1, 68.8.   

Peczuh, M. W.; Synder, N. L. Tetrahedron Lett. 2003, 44, 4057