[(2R,3R,4S,5R,6S)-3,4,5,6-tetraacetyloxyoxan-2-yl]methyl acetate

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

Procedure: To a solution of β-D-glucose pentaacetate (20 g) in CHCl3 (100 mL) was added AlCl3 (3.6 g). After stirring at room temperature, toluene (100 mL) was added, followed by silicic acid (2 g). The mixture was stirred for a few minutes and the precipitate was removed by filtration. The solution was partially concentrated under vacuum and extracted with ice cold water (25 mL). The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g). The mixture was stirred for a few minutes the precipitate was removed by filtration The solution was partially concentrated under vacuum extracted with ice cold water (25 mL) The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g)

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

Procedure: To a solution of β-D-glucose pentaacetate (20 g) in CHCl3 (100 mL) was added AlCl3 (3.6 g). After stirring at room temperature, toluene (100 mL) was added, followed by silicic acid (2 g). The mixture was stirred for a few minutes and the precipitate was removed by filtration. The solution was partially concentrated under vacuum and extracted with ice cold water (25 mL). The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g). The mixture was stirred for a few minutes the precipitate was removed by filtration The solution was partially concentrated under vacuum extracted with ice cold water (25 mL) The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g)

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

Procedure: Hydrobromic acid (30% in acetic acid, 11.85 ml, 55.4 mmol) was added to β-D-glucose pentaacetate (12.01 g, 30.8 mmol) at 0° C. After 10 minutes, the resulting solution was warmed to room temperature and stirred for 4 hours. The reaction mixture was slowly poured, with stirring, into ice water (250 ml) and was stirred until the product solidified. The product was collected by vacuum filtration and washed with cold water. The white solid was dissolved in carbon tetrachloride (60 ml) and washed with H2O (1×20 ml), saturated aqueous NaHCO3 (3×20 ml, until pH=7), H2O (1×20 ml), dried with CaCl2, and poured into cold petroleum ether (250 ml). After 30 min, the crystalline product was collected by vacuum filtration to give the target compound as a white solid (10.0 g, 80%). The reaction mixture was slowly poured was stirred until the product The product was collected by vacuum filtration washed with cold water The white solid was dissolved in carbon tetrachloride (60 ml) washed with H2O (1×20 ml), saturated aqueous NaHCO3 (3×20 ml, until pH=7), H2O (1×20 ml) dried with CaCl2 poured into cold petroleum ether (250 ml) After 30 min the crystalline product was collected by vacuum filtration

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

Procedure: Hydrobromic acid (30% in acetic acid, 11.85 ml, 55.4 mmol) was added to β-D-glucose pentaacetate (12.01 g, 30.8 mmol) at 0° C. After 10 minutes, the resulting solution was warmed to room temperature and stirred for 4 hours. The reaction mixture was slowly poured, with stirring, into ice water (250 ml) and was stirred until the product solidified. The product was collected by vacuum filtration and washed with cold water. The white solid was dissolved in carbon tetrachloride (60 ml) and washed with H2O (1×20 ml), saturated aqueous NaHCO3 (3×20 ml, until pH=7), H2O (1×20 ml), dried with CaCl2, and poured into cold petroleum ether (250 ml). After 30 min, the crystalline product was collected by vacuum filtration to give the target compound as a white solid (10.0 g, 80%). The reaction mixture was slowly poured was stirred until the product The product was collected by vacuum filtration washed with cold water The white solid was dissolved in carbon tetrachloride (60 ml) washed with H2O (1×20 ml), saturated aqueous NaHCO3 (3×20 ml, until pH=7), H2O (1×20 ml) dried with CaCl2 poured into cold petroleum ether (250 ml) After 30 min the crystalline product was collected by vacuum filtration

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

Procedure: 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose (1) (50.0 g, 128 mmol) was dissolved in N,N-dimethylformamide (120 ml) at room temperature and cooled in an ice bath. To this solution was added ammonium acetate (20.0 g, 260 mmol), the ice bath was removed, and the mixture was stirred at room temperature for 21.5 hours. Since the remainder of the starting material was confirmed by thin layer chromatography (TLC), the reaction mixture was cooled in an ice bath, and ammonium acetate (5.0 g, 65 mmol) was added. Then, the ice bath was removed, the reaction mixture was stirred at room temperature for 3 hours, and the disappearance of the starting material was confirmed by TLC. The reaction container was cooled in an ice bath, water (600 ml) was added slowly, and the ice bath was removed. The mixture was extracted 5 times with diethyl ether (400 ml) at room temperature. The combined organic layer was washed with 15% brine (100 ml), dried over magnesium sulfate, and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient; ethyl acetate:n-hexane=40:60→68:32) to give 2,3,4,6-tetra-O-acetyl-D-glucopyranose (2) (38.5 g, 111 mmol, yield 86%) as a colorless transparent oil. As a result of 1H-NMR analysis, it was a mixture of α form:β form at a ratio of about 3:2. cooled in an ice bath the ice bath was removed the reaction mixture was cooled in an ice bath Then, the ice bath was removed the reaction mixture was stirred at room temperature for 3 hours The reaction container was cooled in an ice bath water (600 ml) was added slowly the ice bath was removed The mixture was extracted 5 times with diethyl ether (400 ml) at room temperature The combined organic layer was washed with 15% brine (100 ml) dried over magnesium sulfate filtered the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient; ethyl acetate:n-hexane=40:60→68:32)

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

Procedure: 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose (1) (50.0 g, 128 mmol) was dissolved in N,N-dimethylformamide (120 ml) at room temperature and cooled in an ice bath. To this solution was added ammonium acetate (20.0 g, 260 mmol), the ice bath was removed, and the mixture was stirred at room temperature for 21.5 hours. Since the remainder of the starting material was confirmed by thin layer chromatography (TLC), the reaction mixture was cooled in an ice bath, and ammonium acetate (5.0 g, 65 mmol) was added. Then, the ice bath was removed, the reaction mixture was stirred at room temperature for 3 hours, and the disappearance of the starting material was confirmed by TLC. The reaction container was cooled in an ice bath, water (600 ml) was added slowly, and the ice bath was removed. The mixture was extracted 5 times with diethyl ether (400 ml) at room temperature. The combined organic layer was washed with 15% brine (100 ml), dried over magnesium sulfate, and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient; ethyl acetate:n-hexane=40:60→68:32) to give 2,3,4,6-tetra-O-acetyl-D-glucopyranose (2) (38.5 g, 111 mmol, yield 86%) as a colorless transparent oil. As a result of 1H-NMR analysis, it was a mixture of α form:β form at a ratio of about 3:2. cooled in an ice bath the ice bath was removed the reaction mixture was cooled in an ice bath Then, the ice bath was removed the reaction mixture was stirred at room temperature for 3 hours The reaction container was cooled in an ice bath water (600 ml) was added slowly the ice bath was removed The mixture was extracted 5 times with diethyl ether (400 ml) at room temperature The combined organic layer was washed with 15% brine (100 ml) dried over magnesium sulfate filtered the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient; ethyl acetate:n-hexane=40:60→68:32)

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

Procedure: 1,2,3,4,6-Penta-O-acetyl-β-D-glucopyranose 8 (30 g, 77 mmol) was dissolved in anhydrous DCM (34 mL). 2-Methyl-5-tert-butyl thiophenol (17 mL, 92 mmol, 1.2 eq) were added under stirring. BF3.OEt2 (13.6 mL, 108 mmol, 1.4 eq) was added dropwise and the resulting yellow solution was stirred over night. After completion the solution was diluted with DCM and extracted with saturated aqueous NaHCO3 and H2O, and the organic layer was dried over MgSO4. The solvent was evaporated in vacuo and the residue was dried in high vacuum. The resulting yellow solid was purified by column chromatography on silica gel (cyclohexane/ethyl acetate) to afford 9 (33.4 g, 65.4 mmol, 85%). [α]D20=−8.0° (c=1.0, CHCl3); IR (CHCl3): 2961, 1747, 1366, 1211, 1034, 912 cm−1; 1H-NMR (400 MHz, CDCl3) δ 7.52 (1H, d, J 2.0, Ar—H), 7.25-7.10 (2H, m, Ar—H), 5.19 (1H, dd, J1J2 9.4, 1-H), 5.10-4.98 (2H, m, 4-H, 2-H), 4.64 (1H, d, J 10.6, 1-H), 4.23 (1H, dd, J1 12.2, J2 5.0, 6-Ha), 4.10 (1H, dd, J112.2, J2 1.9, 6-Hb), 3.71-3.63 (1H, m, 5-H), 2.34 (3H, s, CH3), 2.07-2.03 (6H, m, OAc), 2.00-1.96 (6H, m, OAc), 1.29 (9H, s, tBu); 13C-NMR (100 MHz, CDCl3) δ 170.8, 170.3, 169.5, 169.4 (C═O OAc), 149.8, 137.51, 131.47, 130.53, 130.2, 125.8, 87.0 (C-1), 75.9 (C-5), 74.2 (C-3), 70.3 (C-3), 68.3 (C-4), 62.4 (C-6), 31.4 (tBu), 20.89, 20.88, 20.74, 20.70 (OAc), 20.5 (CH3); HRMS (ESI): Calcd for C25H34O9S [M+Na]+ 533.1816. found 533.1832. the resulting yellow solution was stirred over night extracted with saturated aqueous NaHCO3 and H2O the organic layer was dried over MgSO4 The solvent was evaporated in vacuo the residue was dried in high vacuum The resulting yellow solid was purified by column chromatography on silica gel (cyclohexane/ethyl acetate)

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

Procedure: 1,2,3,4,6-Penta-O-acetyl-β-D-glucopyranose 8 (30 g, 77 mmol) was dissolved in anhydrous DCM (34 mL). 2-Methyl-5-tert-butyl thiophenol (17 mL, 92 mmol, 1.2 eq) were added under stirring. BF3.OEt2 (13.6 mL, 108 mmol, 1.4 eq) was added dropwise and the resulting yellow solution was stirred over night. After completion the solution was diluted with DCM and extracted with saturated aqueous NaHCO3 and H2O, and the organic layer was dried over MgSO4. The solvent was evaporated in vacuo and the residue was dried in high vacuum. The resulting yellow solid was purified by column chromatography on silica gel (cyclohexane/ethyl acetate) to afford 9 (33.4 g, 65.4 mmol, 85%). [α]D20=−8.0° (c=1.0, CHCl3); IR (CHCl3): 2961, 1747, 1366, 1211, 1034, 912 cm−1; 1H-NMR (400 MHz, CDCl3) δ 7.52 (1H, d, J 2.0, Ar—H), 7.25-7.10 (2H, m, Ar—H), 5.19 (1H, dd, J1J2 9.4, 1-H), 5.10-4.98 (2H, m, 4-H, 2-H), 4.64 (1H, d, J 10.6, 1-H), 4.23 (1H, dd, J1 12.2, J2 5.0, 6-Ha), 4.10 (1H, dd, J112.2, J2 1.9, 6-Hb), 3.71-3.63 (1H, m, 5-H), 2.34 (3H, s, CH3), 2.07-2.03 (6H, m, OAc), 2.00-1.96 (6H, m, OAc), 1.29 (9H, s, tBu); 13C-NMR (100 MHz, CDCl3) δ 170.8, 170.3, 169.5, 169.4 (C═O OAc), 149.8, 137.51, 131.47, 130.53, 130.2, 125.8, 87.0 (C-1), 75.9 (C-5), 74.2 (C-3), 70.3 (C-3), 68.3 (C-4), 62.4 (C-6), 31.4 (tBu), 20.89, 20.88, 20.74, 20.70 (OAc), 20.5 (CH3); HRMS (ESI): Calcd for C25H34O9S [M+Na]+ 533.1816. found 533.1832. the resulting yellow solution was stirred over night extracted with saturated aqueous NaHCO3 and H2O the organic layer was dried over MgSO4 The solvent was evaporated in vacuo the residue was dried in high vacuum The resulting yellow solid was purified by column chromatography on silica gel (cyclohexane/ethyl acetate)

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

Procedure: To a solution of β-D-glucose pentaacetate (20 g) in CHCl3 (100 mL) was added AlCl3 (3.6 g). After stirring at room temperature, toluene (100 mL) was added, followed by silicic acid (2 g). The mixture was stirred for a few minutes and the precipitate was removed by filtration. The solution was partially concentrated under vacuum and extracted with ice cold water (25 mL). The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g). The mixture was stirred for a few minutes the precipitate was removed by filtration The solution was partially concentrated under vacuum extracted with ice cold water (25 mL) The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g)

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

Procedure: To a solution of β-D-glucose pentaacetate (20 g) in CHCl3 (100 mL) was added AlCl3 (3.6 g). After stirring at room temperature, toluene (100 mL) was added, followed by silicic acid (2 g). The mixture was stirred for a few minutes and the precipitate was removed by filtration. The solution was partially concentrated under vacuum and extracted with ice cold water (25 mL). The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g). The mixture was stirred for a few minutes the precipitate was removed by filtration The solution was partially concentrated under vacuum extracted with ice cold water (25 mL) The organic phase was concentrated to a syrupy mixture and ether was added to precipitate acetochloro-β-D-glucose as a powder (12 g)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(4-ethylphenylmethyl)pyrazole 36 (495 mg) in acetonitrile (2.0 ml) was added N,O-bis(trimethylsilyl)acetamide (1.05 ml), and the mixture was stirred under heating at 60° C. for 2.5 hours under argon atmosphere. The reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure to give crude 4-(4-ethylphenylmethyl)-1-trimethylsilylpyrazole 37, which was used in the subsequent reaction without further purification. (2) The above N-silyl compound 37 was dissolved in dichloroethane (7.0 ml), and added thereto were molecular sieve 4A powder (500 mg), 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose 38 (1.04 g) and trimethylsilyl trifluoromethanesulfonate (0.51 ml). The mixture was stirred under heating at heating at 80° C. for 3 hours under argon atmosphere. The reaction mixture was cooled to room temperature, and insoluble materials were filtered off. Subsequently, the filtrate was poured into a saturated aqueous sodium hydrogen carbonate solution. The mixture was extracted twice with dichloromethane, and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20-50:50) to give 4-(4-ethylphenylmethyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)pyrazole 39 (610 mg) as a colorless semisolid. APCI-Mass m/Z 517 (M+H). (3) From the above tetraacetate compound 39, the desired 4-(4-ethylphenylmethyl)-1-(β-D-glucopyranosyl)pyrazole 40 was prepared in a manner similar to Example 106-(3) as colorless oil. APCI-Mass m/Z 349 (M+H). The reaction mixture was cooled to room temperature the solvent was evaporated under reduced pressure to give crude 4-(4-ethylphenylmethyl)-1-trimethylsilylpyrazole 37, which was used in the subsequent reaction without further purification added The mixture was stirred under heating at heating at 80° C. for 3 hours under argon atmosphere The reaction mixture was cooled to room temperature insoluble materials were filtered off Subsequently, the filtrate was poured into a saturated aqueous sodium hydrogen carbonate solution The mixture was extracted twice with dichloromethane dried over sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20-50:50)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(4-ethylphenylmethyl)pyrazole 36 (495 mg) in acetonitrile (2.0 ml) was added N,O-bis(trimethylsilyl)acetamide (1.05 ml), and the mixture was stirred under heating at 60° C. for 2.5 hours under argon atmosphere. The reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure to give crude 4-(4-ethylphenylmethyl)-1-trimethylsilylpyrazole 37, which was used in the subsequent reaction without further purification. (2) The above N-silyl compound 37 was dissolved in dichloroethane (7.0 ml), and added thereto were molecular sieve 4A powder (500 mg), 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose 38 (1.04 g) and trimethylsilyl trifluoromethanesulfonate (0.51 ml). The mixture was stirred under heating at heating at 80° C. for 3 hours under argon atmosphere. The reaction mixture was cooled to room temperature, and insoluble materials were filtered off. Subsequently, the filtrate was poured into a saturated aqueous sodium hydrogen carbonate solution. The mixture was extracted twice with dichloromethane, and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20-50:50) to give 4-(4-ethylphenylmethyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)pyrazole 39 (610 mg) as a colorless semisolid. APCI-Mass m/Z 517 (M+H). (3) From the above tetraacetate compound 39, the desired 4-(4-ethylphenylmethyl)-1-(β-D-glucopyranosyl)pyrazole 40 was prepared in a manner similar to Example 106-(3) as colorless oil. APCI-Mass m/Z 349 (M+H). The reaction mixture was cooled to room temperature the solvent was evaporated under reduced pressure to give crude 4-(4-ethylphenylmethyl)-1-trimethylsilylpyrazole 37, which was used in the subsequent reaction without further purification added The mixture was stirred under heating at heating at 80° C. for 3 hours under argon atmosphere The reaction mixture was cooled to room temperature insoluble materials were filtered off Subsequently, the filtrate was poured into a saturated aqueous sodium hydrogen carbonate solution The mixture was extracted twice with dichloromethane dried over sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20-50:50)