(3R,4S,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-ol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture that consists of 54.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-glucopyranose, 0.55 g (5 mmol) of tetramethylammonium chloride and 12.42 g (100 mmol) of DBN in 350 ml of diethoxymethane is cooled to 0° C. At 0° C., 44 g (150 mmol) of 11-bromoundecanoic acid-ethyl ester, dissolved in 50 ml of benzene, is added in drops over 30 minutes while being stirred vigorously. It is stirred for two hours at 20° C. 250 ml of methyl-tert-butyl ether is added, solid is filtered out, and the filtrate is evaporated to the dry state in a vacuum. The residue is taken up in 500 ml of ethanol/50 ml of water. 60 ml of 50% aqueous sodium hydroxide solution is added, and it is refluxed for five hours. It is cooled to 0° C., set at pH 8 with 10% aqueous hydrochloric acid, and then the solvent is distilled off (vacuum). The residue is taken up in 300 ml of water and 500 ml of dichloromethane, and the pH of the aqueous phase is set at 2 while being stirred (10% aqueous hydrochloric acid). The organic phase is separated, and the aqueous phase is extracted once more with 200 ml of dichloromethane. The combined organic phases are dried on magnesium sulfate, the solvent is distilled off in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n-hexane/ethanol/acetic acid=20:5:3:0.5). The product-containing fractions are concentrated by evaporation, dissolved in 400 ml of ethyl acetate and shaken out three times with 200 ml of water. Then, the organic phase is separated and evaporated to the dry state in a vacuum. is added in drops over 30 minutes It is stirred for two hours at 20° C solid is filtered out the filtrate is evaporated to the dry state in a vacuum 60 ml of 50% aqueous sodium hydroxide solution is added it is refluxed for five hours It is cooled to 0° C. the solvent is distilled off (vacuum) while being stirred (10% aqueous hydrochloric acid) The organic phase is separated the aqueous phase is extracted once more with 200 ml of dichloromethane The combined organic phases are dried on magnesium sulfate the solvent is distilled off in a vacuum the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n-hexane/ethanol/acetic acid=20:5:3:0.5) The product-containing fractions are concentrated by evaporation dissolved in 400 ml of ethyl acetate shaken out three times with 200 ml of water Then, the organic phase is separated evaporated to the dry state in a vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture that consists of 54.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-glucopyranose, 1.39 g (5 mmol) of tetrabutylammonium chloride and 11.22 g of potassium-t-butoxide (100 mmol) in 500 ml of diethoxymethane is cooled to 0° C. At 0° C., 29.3 g (150 mmol) of bromoacetic acid-tert-butyl ester is added in drops over 20 minutes while being stirred vigorously. It is stirred for 0.5 hour at 0° C. 250 toluene is added, the organic phase is separated, and the aqueous phase is extracted twice with 150 ml of toluene. The solvent of the combined organic phases is washed with water, dried on sodium sulfate, dessicant is filtered off, and it is distilled off in a vacuum. The residue is taken up in 400 ml of methanol. 50 ml of 50% aqueous sodium hydroxide solution is added, and it is refluxed for 0.5 hour. It is cooled to 0° C., set at pH 8 with 10% aqueous hydrochloric acid, and then the solvent is distilled off (vacuum). The residue is taken up in 300 ml of water and 500 ml of dichloromethane, and the pH of the aqueous phase is set at 2 while being stirred (10% aqueous hydrochloric acid). The organic phase is separated, and the aqueous phase is extracted once more with 200 ml of dichloromethane. The combined organic phases are dried on magnesium sulfate, the solvent is distilled off in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n-hexane/ethanol/acetic acid=20:5:3:0.5). The product-containing fractions are concentrated by evaporation, dissolved in 400 ml of ethyl acetate and shaken out three times with 200 ml of water. Then, the organic phase is separated and evaporated to the dry state in a vacuum. It is stirred for 0.5 hour at 0° C the organic phase is separated the aqueous phase is extracted twice with 150 ml of toluene The solvent of the combined organic phases is washed with water dried on sodium sulfate, dessicant is filtered off it is distilled off in a vacuum 50 ml of 50% aqueous sodium hydroxide solution is added it is refluxed for 0.5 hour It is cooled to 0° C. the solvent is distilled off (vacuum) while being stirred (10% aqueous hydrochloric acid) The organic phase is separated the aqueous phase is extracted once more with 200 ml of dichloromethane The combined organic phases are dried on magnesium sulfate the solvent is distilled off in a vacuum the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n-hexane/ethanol/acetic acid=20:5:3:0.5) The product-containing fractions are concentrated by evaporation dissolved in 400 ml of ethyl acetate shaken out three times with 200 ml of water Then, the organic phase is separated evaporated to the dry state in a vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture that consists of 54.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-glucopyranose, 1.39 g (5 mmol) of tetrabutylammonium chloride and 11.22 g of potassium-t-butoxide (100 mmol) in 500 ml of diethoxymethane is cooled to 0° C. At 0° C., 29.3 g (150 mmol) of bromoacetic acid-tert-butyl ester is added in drops over 20 minutes while being stirred vigorously. It is stirred for 0.5 hour at 0° C. 250 toluene is added, the organic phase is separated, and the aqueous phase is extracted twice with 150 ml of toluene. The solvent of the combined organic phases is washed with water, dried on sodium sulfate, dessicant is filtered off, and it is distilled off in a vacuum. The residue is taken up in 400 ml of methanol. 50 ml of 50% aqueous sodium hydroxide solution is added, and it is refluxed for 0.5 hour. It is cooled to 0° C., set at pH 8 with 10% aqueous hydrochloric acid, and then the solvent is distilled off (vacuum). The residue is taken up in 300 ml of water and 500 ml of dichloromethane, and the pH of the aqueous phase is set at 2 while being stirred (10% aqueous hydrochloric acid). The organic phase is separated, and the aqueous phase is extracted once more with 200 ml of dichloromethane. The combined organic phases are dried on magnesium sulfate, the solvent is distilled off in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n-hexane/ethanol/acetic acid=20:5:3:0.5). The product-containing fractions are concentrated by evaporation, dissolved in 400 ml of ethyl acetate and shaken out three times with 200 ml of water. Then, the organic phase is separated and evaporated to the dry state in a vacuum. It is stirred for 0.5 hour at 0° C the organic phase is separated the aqueous phase is extracted twice with 150 ml of toluene The solvent of the combined organic phases is washed with water dried on sodium sulfate, dessicant is filtered off it is distilled off in a vacuum 50 ml of 50% aqueous sodium hydroxide solution is added it is refluxed for 0.5 hour It is cooled to 0° C. the solvent is distilled off (vacuum) while being stirred (10% aqueous hydrochloric acid) The organic phase is separated the aqueous phase is extracted once more with 200 ml of dichloromethane The combined organic phases are dried on magnesium sulfate the solvent is distilled off in a vacuum the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n-hexane/ethanol/acetic acid=20:5:3:0.5) The product-containing fractions are concentrated by evaporation dissolved in 400 ml of ethyl acetate shaken out three times with 200 ml of water Then, the organic phase is separated evaporated to the dry state in a vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture that consists of 54.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-glucopyranose, 1.39 g (5 mmol) of tetrabutylammonium chloride and 15.22 g (100 mmol) of DBU in 300 ml of diethoxymethane is cooled to 0° C. At 0° C., 78 g (150 mmol) of 5-tosyloxy-pentanecarboxylic acid-tert-butyl ester, dissolved in 40 ml of tetrahydrofaran, is added in drops over 30 minutes while being stirred vigorously. It is stirred for 3 hours at 0° C. 300 ml of MTB (methyl-tert-butyl ether) is added, solid is filtered out, and the filtrate is evaporated to the dry state in a vacuum. The residue is taken up in 500 ml of methanol. 50 ml of 50% aqueous sodium hydroxide solution is added, and it is refluxed for one hour. It is cooled to 0° C., set at pH 8 with 10% aqueous hydrochloric acid, and then the solvent is distilled off (vacuum). The residue is taken up in 300 ml of water and 500 ml of ethyl acetate, and the pH of the aqueous phase is set at 2 while being stirred (10% aqueous hydrochloric acid). The organic phase is separated, and the aqueous phase is extracted once more with 200 ml of dichloromethane. The combined organic phases are dried on magnesium sulfate, the solvent is distilled off in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n=hexane/ethanol/acetic acid=20:5:3:0.5). The product-containing fractions are concentrated by evaporation, dissolved in 400 ml of ethyl acetate, and shaken out three times with 200 ml of water. Then, the organic phase is separated and evaporated to the dry state in a vacuum. is added in drops over 30 minutes It is stirred for 3 hours at 0° C solid is filtered out the filtrate is evaporated to the dry state in a vacuum 50 ml of 50% aqueous sodium hydroxide solution is added it is refluxed for one hour It is cooled to 0° C. the solvent is distilled off (vacuum) while being stirred (10% aqueous hydrochloric acid) The organic phase is separated the aqueous phase is extracted once more with 200 ml of dichloromethane The combined organic phases are dried on magnesium sulfate the solvent is distilled off in a vacuum the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n=hexane/ethanol/acetic acid=20:5:3:0.5) The product-containing fractions are concentrated by evaporation dissolved in 400 ml of ethyl acetate shaken out three times with 200 ml of water Then, the organic phase is separated evaporated to the dry state in a vacuum

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

Procedure: To a round bottom flask containing a solution of (S)-3-(5-Chloro-2-methoxy-phenyl)-1-chloromethyl-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one (S)-IV) (0.486 g, 1.2 mmol) in anhydrous acetonitrile (9 mL) was added 2,3,4,6-tetra-O-benzyl-D-glucopyranose (V; 0.648 g, 1.2 mmol) and cesium carbonate (0.390 g, 1.2 mmol). The reaction mixture was allowed to stir at room temperature overnight. The solvent was then removed, and the crude product was purified via flash chromatography (silica gel, 5:1 hexanes:ethyl acetate) to give a 1:1 mixture of α and β anomers of the title compound (0.768 g, 71%). 1H NMR (CDCl3, 400 MHz): δ 7.79 (dd, 2H, J=5.1 Hz, 1.8 Hz), 7.37-7.12 (m, 48H), 6.66 (m, 2H), 5.66 (d, 1H, J=11.0 Hz), 5.34 (m, 2H), 5.08 (d, 1H, J=3.7 Hz), 4.89-4.73 (m, 9H), 4.66-4.44 (m, 9H), 3.79 (m, 3H), 3.73-3.59 (m, 6H), 3.55-3.49 (m, 3H), 3.38 (d, 6H, J=4.1 Hz). The solvent was then removed the crude product was purified via flash chromatography (silica gel, 5:1 hexanes:ethyl acetate) to give

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

Procedure: 3.0 g (5.5 mmol) of 2,3,4,6-tetra-O-benzyl-D-glucopyranose were dissolved in 30 ml of anhydrous methylene chloride and the solution was stirred with 1.45 ml (2.11 g; 16.5 mmol) of oxalyl dichloride and 0.3 ml of dimethylformamide at room temperature. After one hour, the solution was concentrated under a high vacuum, the residue was taken up in 10 ml of methylene chloride and the mixture was filtered over about 10 g of silica gel. Renewed concentration gave 2.48 g (80%) of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl chloride as a colorless syrup. The crude product was taken up in 20 ml of anhydrous acetonitrile and the mixture was heated under reflux with 3.0 g (38 mmol) of potassium hydrogen fluoride (24 hours at 100° C., dried over P2O5) for 8 hours. It was possible to purify the crude product by column chromatography on silica gel (methylene chloride/ether, 20:1). Yield: 1.1 g (47%) of 2,3,4,6 -tetra-O-benzyl-α-D-glucopyranosyl fluoride. the solution was concentrated under a high vacuum the mixture was filtered over about 10 g of silica gel Renewed concentration

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

Procedure: 3.0 g (5.5 mmol) of 2,3,4,6-tetra-O-benzyl-D-glucopyranose were dissolved in 30 ml of anhydrous methylene chloride and the solution was stirred with 1.45 ml (2.11 g; 16.5 mmol) of oxalyl dichloride and 0.3 ml of dimethylformamide at room temperature. After one hour, the solution was concentrated under a high vacuum, the residue was taken up in 10 ml of methylene chloride and the mixture was filtered over about 10 g of silica gel. Renewed concentration gave 2.48 g (80%) of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl chloride as a colorless syrup. The crude product was taken up in 20 ml of anhydrous acetonitrile and the mixture was heated under reflux with 3.0 g (38 mmol) of potassium hydrogen fluoride (24 hours at 100° C., dried over P2O5) for 8 hours. It was possible to purify the crude product by column chromatography on silica gel (methylene chloride/ether, 20:1). Yield: 1.1 g (47%) of 2,3,4,6 -tetra-O-benzyl-α-D-glucopyranosyl fluoride. the solution was concentrated under a high vacuum the mixture was filtered over about 10 g of silica gel Renewed concentration

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,3,4,6-Tetra-O-benzyl-D-glucopyranose (1.0 g, 1.9 mmol) was dissolved in anhydrous DCM (6 mL) and anhydrous DMF (0.4 mL) under argon. The resulting solution was stirred at 0° C. Oxalyl bromide (4 mL, 2M in DCM, 24 mmol) was added dropwise over a 5 min period . The reaction was stirred at RT. After a 40 min period, t.l.c. (petrol:ethyl acetate, 2:1) indicated the formation of a major product (Rf 0.7). The reaction was cooled to 0° C. and quenched with ice cold water (30 mL) added over a 5 min period. The reaction was partitioned between DCM (20 mL) and water. The aqueous layer was re-extracted with DCM (3×20 mL), the combined organic layers were washed with brine (40 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title product (1.10 g, 95%) as a crude yellow oil; δH (400 MHz, CDCl3), 3.57 (1H, dd, J1,2 3.5 Hz, J2,3 9.1 Hz, H-2), 3.68 (1H, dd, J5,6 2.1 Hz, J6,6′ 11.0 Hz, H-6), 3.79-3.84 (2H, m, H-4, H-6′), 4.07 (1H, at, J9.1 Hz, H-3), 4.07-4.11 (1H, m, H-5), 4.47-4.62 (3H, m, PhCH2), 4.74 (s, 2H, PhCH2), 4.84-4.89 (2H, m, PhCH2), 5.10 (1H, d, J11.1 Hz, PhCH2), 6.46 (1H, d, H-1), 7.15-7.41 (20H, m, Ar—H). The reaction was stirred at RT The reaction was cooled to 0° C. quenched with ice cold water (30 mL) added over a 5 min period The reaction was partitioned between DCM (20 mL) and water The aqueous layer was re-extracted with DCM (3×20 mL) the combined organic layers were washed with brine (40 mL) dried (MgSO4) filtered concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,3,4,6-Tetra-O-benzyl-D-glucopyranose (1.0 g, 1.9 mmol) was dissolved in anhydrous DCM (6 mL) and anhydrous DMF (0.4 mL) under argon. The resulting solution was stirred at 0° C. Oxalyl bromide (4 mL, 2M in DCM, 24 mmol) was added dropwise over a 5 min period . The reaction was stirred at RT. After a 40 min period, t.l.c. (petrol:ethyl acetate, 2:1) indicated the formation of a major product (Rf 0.7). The reaction was cooled to 0° C. and quenched with ice cold water (30 mL) added over a 5 min period. The reaction was partitioned between DCM (20 mL) and water. The aqueous layer was re-extracted with DCM (3×20 mL), the combined organic layers were washed with brine (40 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title product (1.10 g, 95%) as a crude yellow oil; δH (400 MHz, CDCl3), 3.57 (1H, dd, J1,2 3.5 Hz, J2,3 9.1 Hz, H-2), 3.68 (1H, dd, J5,6 2.1 Hz, J6,6′ 11.0 Hz, H-6), 3.79-3.84 (2H, m, H-4, H-6′), 4.07 (1H, at, J9.1 Hz, H-3), 4.07-4.11 (1H, m, H-5), 4.47-4.62 (3H, m, PhCH2), 4.74 (s, 2H, PhCH2), 4.84-4.89 (2H, m, PhCH2), 5.10 (1H, d, J11.1 Hz, PhCH2), 6.46 (1H, d, H-1), 7.15-7.41 (20H, m, Ar—H). The reaction was stirred at RT The reaction was cooled to 0° C. quenched with ice cold water (30 mL) added over a 5 min period The reaction was partitioned between DCM (20 mL) and water The aqueous layer was re-extracted with DCM (3×20 mL) the combined organic layers were washed with brine (40 mL) dried (MgSO4) filtered concentrated in vacuo

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

Procedure: With similar method described in Step 3 of Example 92, (5-bromo-2-chloro-4-methoxybenzyloxy)triisopropylsilane (compound 89, 27.2 g, 66.7 mmol) and 2,3,4,6-tetra-O-benzyl-D-glucopyranose (compound 2, 30.0 g, 55.6 mmol) were converted to title compound (22.6 g, 59%, ca. 8:1 mixture of anomers (13:0) as a white solid.

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

Procedure: With similar method described in Step 3 of Example 92, (5-bromo-2,4-dichlorobenzyloxy)triisopropylsilane (compound 82, 41.7 g, 101 mmol) and 2,3,4,6-tetra-O-benzyl-D-glucopyranose (compound 2, 45.4 g, 84.0 mmol) were converted to title compound (47.6 g, 81%, ca. 8:1 mixture of anomers (13:0) as a white solid.

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

Procedure: With similar method described in Step 3 of Example 92, ((3-bromonaphthalen-1-yl)methoxy)triisopropylsilane (compound 76, 18.0 g, 45.6 mmol) and 2,3,4,6-tetra-O-benzyl-D-glucopyranose (2, 20.5 g, 38.0 mmol) were converted to title compound (23.3 g, 90%, ca. 2:1 mixture of anomers (13:0) as a white solid.