(2R,3R,4S)-2-[(1R)-1,2-dihydroxyethyl]oxolane-3,4-diol

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

Procedure: D-Glucitol (Aldrich, 1150 g, 6.31 mol) was suspended in aqueous 3M H2SO4 (550 mL) and heated at reflux with stirring under N2 overnight. The dark brown solution was cooled and neutralized using Amberlite® IRA-93 resin (OH-, ~4 L) Rohm and Haas, (Phil., Pa.). The resin was removed by filtration; the filtrate was decolorized using activated carbon (4 g) which was subsequently removed by filtration. heated at reflux The dark brown solution was cooled The resin was removed by filtration was subsequently removed by filtration

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

Procedure: D-Glucitol (Aldrich, 1150 g, 6.31 mol) was suspended in aqueous 3M H2SO4 (550 mL) and heated at reflux with stirring under N2 overnight. The dark brown solution was cooled and neutralized using Amberlite® IRA-93 resin (OH-, ~4 L) Rohm and Haas, (Phil., Pa.). The resin was removed by filtration; the filtrate was decolorized using activated carbon (4 g) which was subsequently removed by filtration. heated at reflux The dark brown solution was cooled The resin was removed by filtration was subsequently removed by filtration

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

Procedure: 1,4-Anhydro-D-glucitol may be prepared using the procedure disclosed in Acta Chem. Scand., B35, 441-449 (1981), whereby D-sorbitol is heated with an aqueous mineral acid such as sulfuric acid. The L-enantiomer, 1,4-anhydro-L-glucitol, may be prepared from L-glucitol by an analogous procedure. L-glucitol may be prepared by sodium borohydride reduction of L-glucose. The D and L enantiomers may simply be combined to form a 1,4-anhydro-DL-glucitol mixture.

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

Procedure: 1,4-Anhydro-D-glucitol may be prepared using the procedure disclosed in Acta Chem. Scand., B35, 441-449 (1981), whereby D-sorbitol is heated with an aqueous mineral acid such as sulfuric acid. The L-enantiomer, 1,4-anhydro-L-glucitol, may be prepared from L-glucitol by an analogous procedure. L-glucitol may be prepared by sodium borohydride reduction of L-glucose. The D and L enantiomers may simply be combined to form a 1,4-anhydro-DL-glucitol mixture.

Conditions: temp:104.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of D-sorbitol (1) (4.0 kg), water (560 mL) and H2SO4 (50 mL) was heated to a melt (104° C.) and stirred. After 20 h, 25 mL of H2SO4 was added. After a farther 22 h, 25 mL of H2SO4 was added. After a further 32 h, the mixture was cooled to ambient temperature, neutralized carefully with solid Na2CO3 and stirred for 30 min. i-PrOH (12 L) was added, followed by anhydrous Na2SO4 (4 kg). The mixture was filtered and the solid was washed with i-PrOH (6 L) and EtOH (3 L). The filtrate was treated with activated charcoal (100 g), filtered through Celite, rinsing with 1.2 L each of i-PrOH and EtOH, then concentrated. Toluene (6 L) was added to the residue, and the mixture was concentrated in vacuo with heating to effect azeotropic removal of water. EtOH (10 L) was added to the solid residue with beating to effect dissolution. The solution was concentrated and cooled to ambient temperature to give a suspension (6 L). The solid was isolated by filtration, washed with cold EtOH (4 L) and dried. Recrystallization of the crude product (1.9 kg) from hot EtOH provided 2 (1693 g) as a white solid, mp 112-112.5° C., [α]23D−22.9°(c 0.5, H2O). The 13C NMR spectrum of this compound agreed with that reported by Duclos et al., Synthesis, page 1087 (1994). After a farther 22 h After a further 32 h the mixture was cooled to ambient temperature was added The mixture was filtered the solid was washed with i-PrOH (6 L) and EtOH (3 L) The filtrate was treated with activated charcoal (100 g) filtered through Celite rinsing with 1.2 L each of i-PrOH and EtOH concentrated Toluene (6 L) was added to the residue the mixture was concentrated in vacuo with heating removal of water EtOH (10 L) was added to the solid residue dissolution The solution was concentrated cooled to ambient temperature

Conditions: temp:104.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of D-sorbitol (1) (4.0 kg), water (560 mL) and H2SO4 (50 mL) was heated to a melt (104° C.) and stirred. After 20 h, 25 mL of H2SO4 was added. After a farther 22 h, 25 mL of H2SO4 was added. After a further 32 h, the mixture was cooled to ambient temperature, neutralized carefully with solid Na2CO3 and stirred for 30 min. i-PrOH (12 L) was added, followed by anhydrous Na2SO4 (4 kg). The mixture was filtered and the solid was washed with i-PrOH (6 L) and EtOH (3 L). The filtrate was treated with activated charcoal (100 g), filtered through Celite, rinsing with 1.2 L each of i-PrOH and EtOH, then concentrated. Toluene (6 L) was added to the residue, and the mixture was concentrated in vacuo with heating to effect azeotropic removal of water. EtOH (10 L) was added to the solid residue with beating to effect dissolution. The solution was concentrated and cooled to ambient temperature to give a suspension (6 L). The solid was isolated by filtration, washed with cold EtOH (4 L) and dried. Recrystallization of the crude product (1.9 kg) from hot EtOH provided 2 (1693 g) as a white solid, mp 112-112.5° C., [α]23D−22.9°(c 0.5, H2O). The 13C NMR spectrum of this compound agreed with that reported by Duclos et al., Synthesis, page 1087 (1994). After a farther 22 h After a further 32 h the mixture was cooled to ambient temperature was added The mixture was filtered the solid was washed with i-PrOH (6 L) and EtOH (3 L) The filtrate was treated with activated charcoal (100 g) filtered through Celite rinsing with 1.2 L each of i-PrOH and EtOH concentrated Toluene (6 L) was added to the residue the mixture was concentrated in vacuo with heating removal of water EtOH (10 L) was added to the solid residue dissolution The solution was concentrated cooled to ambient temperature

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

Procedure: 23.8 g of nicotinoyl chloride-hydrochloride are added in portions in the course of 15 minutes to a suspension of 5.0 g of 1,4-anhydro-D-glucitol (Arlitan) in 30 g of triethylamine and 100 ml of methylene chloride, at 40°, whilst stirring and with the exclusion of atmospheric moisture. After the reaction mixture has been allowed to react for a further 30 minutes, it is filtered and the bulk of the methylene chloride is distilled off from the filtrate. The residue which is thus formed from the filtrate is dissolved in methylene chloride and the solution is washed with water. After drying over sodium sulphate, evaporating under a waterpump vacuum and degassing the residue under a high vacuum, pure 2,3,5,6-tetra-O-nicotinoyl-1,4-anhydro-D-glucitol is obtained as a viscous, brownish oil which has an optical rotation [α]D20 = + 16° ± 1° (c = 1.099 in chloroform), IR: carbonyl band at 1,730 cm-1, and a Rf value of 0.26 on silica gel thin layer plates in the system: methylene chloride/ethyl acetate (85:15). to react for a further 30 minutes it is filtered the bulk of the methylene chloride is distilled off from the filtrate The residue which is thus formed from the filtrate the solution is washed with water After drying over sodium sulphate evaporating under a waterpump vacuum degassing the residue under a high vacuum

Conditions: temp:104.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of D-sorbitol (1) (4.0 kg), water (560 mL) and H2SO4 (50 mL) was heated to a melt (104° C.) and stirred. After 20 h, 25 mL of H2SO4 was added. After a further 22 h, 25 mL of H2SO4 was added. After a further 32 h, the mixture was cooled to ambient temperature, neutralized carefully with solid Na2CO3 and stirred for 30 min. i-PrOH (12 L) was added, followed by anhydrous Na2SO4 (4 kg). The mixture was filtered and the solid was washed with i-PrOH (6 L) and EtOH (3 L). The filtrate was treated with activated charcoal (100 g), filtered through Celite, rinsing with 1.2 L each of i-PrOH and EtOH, then concentrated. Toluene (6 L) was added to the residue, and the mixture was concentrated in vacuo with heating to effect azeotropic removal of water. EtOH (10 L) was added to the solid residue with heating to effect dissolution. The solution was concentrated and cooled to ambient temperature to give a suspension (6 L). The solid was isolated by filtration, washed with cold EtOH (4 L) and dried. Recrystallization of the crude product (1.9 kg) from hot EtOH provided 2 (1693 g) as a white solid, mp112-112.5° C., [α]23D-22.9 ° (c 0.5, H2O). The 13C NMR spectrum of this compound agreed with that reported by Duclos et al., Synthesis, page 1087 (1994). After a further 22 h After a further 32 h the mixture was cooled to ambient temperature was added The mixture was filtered the solid was washed with i-PrOH (6 L) and EtOH (3 L) The filtrate was treated with activated charcoal (100 g) filtered through Celite rinsing with 1.2 L each of i-PrOH and EtOH concentrated Toluene (6 L) was added to the residue the mixture was concentrated in vacuo with heating removal of water EtOH (10 L) was added to the solid residue with heating dissolution The solution was concentrated cooled to ambient temperature

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

Procedure: D-Glucitol (Aldrich, 1150 g, 6.31 mol) was suspended in aqueous 3M H2SO4 (550 mL) and heated at reflux with stirring under N2 overnight. The dark brown solution was cooled and neutralized using Amberlite® IRA-93 resin (OH-, ~4 L) Rohm and Haas, (Phil., Pa.). The resin was removed by filtration; the filtrate was decolorized using activated carbon (4 g) which was subsequently removed by filtration. heated at reflux The dark brown solution was cooled The resin was removed by filtration was subsequently removed by filtration