(3aR,4R,6aS)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-ol

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

Procedure: (3R,3aR,6aS)-Hexahydrofuro[2,3-b]furan-3-ol (125 mg) obtained in Example 25 was dissolved in toluene (2 mL). Benzoic acid (214 mg), a 40 wt % solution (705 mg) of diethyl azodicarboxylate in toluene, and triphenylphosphine (416 mg) were added. The mixture was stirred overnight. After the reaction, 10% of the solution was purified by flash chromatography to give the title compound (12 mg) (88% ee), which was almost a pure anti-form. was purified by flash chromatography

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

Procedure: A mixture (287 g, content 69.7%, 1.54 mol) containing (3R,3aS,6aR)-hexahydrofuro[2,3,b]furan-3-ol, (3S,3aS,6aR)-hexahydrofuro[2,3,b]furan-3-ol, (3S,3aR,6aS)-hexahydrofuro[2,3,b]furan-3-ol and (3R,3aR,6aS)-hexahydrofuro[2,3,b]furan-3-ol obtained by the same method as in Example 4 was dissolved in methyl ethyl ketone (2000 ml), and to this was added a solution prepared by dissolving dipotassium hydrogen phosphate (937 g, 5.38 mmol) in water (600 ml). To this was added 2,2,6,6-tetramethylpiperidinyl-1-oxy (1.2 g, 7.7 mmol), and the mixture was cooled to about 0° C. A sodium hypochlorite aqueous solution (1490 g, effective chlorine concentration 13.5%, 2.83 mol) was dropped at 15° C. or less, and the mixture was stirred for 1 hour. After completion of the reaction, a 10% sodium thiosulfate aqueous solution (220 ml) was added and the mixture was stirred for 30 minutes and neutralized with 85% phosphoric acid, and liquid-partitioned. Further, the aqueous layer was extracted twice with methyl ethyl ketone (1000 ml) and the organic layers were combined. To the organic layer was added 1.0 g of hydroquinone, and 3000 ml of the solvent was distilled off. To the concentrated residue was added anhydrous magnesium sulfate (30 g), sodium bicarbonate (20 g) and activated carbon (10 g) and the mixture was stirred for 1 hour. Magnesium sulfate, sodium bicarbonate and activated carbon were filtrated, then, 2-propanol (3000 ml) was added, and the solvent (3300 ml) was distilled off, then, recrystallization was carried out to obtain a white crystal (3aR,6aR)-tetrahydrofuro[2,3-b]furan-3(2H)-one (156.5 g, purity 99.5%, yield 79.1%). At this stage, the enantiomer excess was 100% ee. obtained by the same method as in Example 4 to this was added a solution prepared To this was added 2,2,6,6-tetramethylpiperidinyl-1-oxy (1.2 g, 7.7 mmol) After completion of the reaction the mixture was stirred for 30 minutes liquid-partitioned Further, the aqueous layer was extracted twice with methyl ethyl ketone (1000 ml) To the organic layer was added 1.0 g of hydroquinone, and 3000 ml of the solvent was distilled off To the concentrated residue was added anhydrous magnesium sulfate (30 g), sodium bicarbonate (20 g) and activated carbon (10 g) the mixture was stirred for 1 hour Magnesium sulfate, sodium bicarbonate and activated carbon were filtrated 2-propanol (3000 ml) was added the solvent (3300 ml) was distilled off recrystallization

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

Procedure: A mixture (287 g, content 69.7%, 1.54 mol) containing (3R,3aS,6aR)-hexahydrofuro[2,3,b]furan-3-ol, (3S,3aS,6aR)-hexahydrofuro[2,3,b]furan-3-ol, (3S,3aR,6aS)-hexahydrofuro[2,3,b]furan-3-ol and (3R,3aR,6aS)-hexahydrofuro[2,3,b]furan-3-ol obtained by the same method as in Example 4 was dissolved in methyl ethyl ketone (2000 ml), and to this was added a solution prepared by dissolving dipotassium hydrogen phosphate (937 g, 5.38 mmol) in water (600 ml). To this was added 2,2,6,6-tetramethylpiperidinyl-1-oxy (1.2 g, 7.7 mmol), and the mixture was cooled to about 0° C. A sodium hypochlorite aqueous solution (1490 g, effective chlorine concentration 13.5%, 2.83 mol) was dropped at 15° C. or less, and the mixture was stirred for 1 hour. After completion of the reaction, a 10% sodium thiosulfate aqueous solution (220 ml) was added and the mixture was stirred for 30 minutes and neutralized with 85% phosphoric acid, and liquid-partitioned. Further, the aqueous layer was extracted twice with methyl ethyl ketone (1000 ml) and the organic layers were combined. To the organic layer was added 1.0 g of hydroquinone, and 3000 ml of the solvent was distilled off. To the concentrated residue was added anhydrous magnesium sulfate (30 g), sodium bicarbonate (20 g) and activated carbon (10 g) and the mixture was stirred for 1 hour. Magnesium sulfate, sodium bicarbonate and activated carbon were filtrated, then, 2-propanol (3000 ml) was added, and the solvent (3300 ml) was distilled off, then, recrystallization was carried out to obtain a white crystal (3aR,6aR)-tetrahydrofuro[2,3-b]furan-3(2H)-one (156.5 g, purity 99.5%, yield 79.1%). At this stage, the enantiomer excess was 100% ee. obtained by the same method as in Example 4 to this was added a solution prepared To this was added 2,2,6,6-tetramethylpiperidinyl-1-oxy (1.2 g, 7.7 mmol) After completion of the reaction the mixture was stirred for 30 minutes liquid-partitioned Further, the aqueous layer was extracted twice with methyl ethyl ketone (1000 ml) To the organic layer was added 1.0 g of hydroquinone, and 3000 ml of the solvent was distilled off To the concentrated residue was added anhydrous magnesium sulfate (30 g), sodium bicarbonate (20 g) and activated carbon (10 g) the mixture was stirred for 1 hour Magnesium sulfate, sodium bicarbonate and activated carbon were filtrated 2-propanol (3000 ml) was added the solvent (3300 ml) was distilled off recrystallization

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

Procedure: (3R,3aR,6aS)-Hexahydrofuro[2,3-b]furan-3-ol (125 mg) obtained in Example 25 was dissolved in toluene (2 mL). Benzoic acid (214 mg), a 40 wt % solution (705 mg) of diethyl azodicarboxylate in toluene, and triphenylphosphine (416 mg) were added. The mixture was stirred overnight. After the reaction, 10% of the solution was purified by flash chromatography to give the title compound (12 mg) (88% ee), which was almost a pure anti-form. was purified by flash chromatography