2,3,4a,6,7,8a-hexahydro-[1,4]dioxino[2,3-b][1,4]dioxine-2,3,6,7-tetrol

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

Procedure: Glyoxal trimeric dihydrate (15.8 g, 75 mmol) was added to a mixture of N-phenylmethyl-N′-(2-pyridinyl)-1,2-ethanediamine (Description 146, 5.7 g, 25 mmol) and hydrochloric acid (2N, 100 mL) and the mixture was stirred at room temperature for 24 hours. Further glyoxal trimeric dihydrate (5.3 g, 25 mmol) was added and the mixture was stirred at room temperature for 20 hours. The mixture was basified with aqueous sodium hydroxide (4M) and extracted with ethyl acetate (2×200 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (40:60 increasing to 30:70), to give the title compound as a light brown oil (3.6 g, 54%). m/z (ES+) 268 (M+1). the mixture was stirred at room temperature for 20 hours extracted with ethyl acetate (2×200 mL) The combined organic fractions were dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (40:60 increasing to 30:70)

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

Procedure: Glyoxal trimeric dihydrate (15.8 g, 75 mmol) was added to a mixture of N-phenylmethyl-N′-(2-pyridinyl)-1,2-ethanediamine (Description 146, 5.7 g, 25 mmol) and hydrochloric acid (2N, 100 mL) and the mixture was stirred at room temperature for 24 hours. Further glyoxal trimeric dihydrate (5.3 g, 25 mmol) was added and the mixture was stirred at room temperature for 20 hours. The mixture was basified with aqueous sodium hydroxide (4M) and extracted with ethyl acetate (2×200 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (40:60 increasing to 30:70), to give the title compound as a light brown oil (3.6 g, 54%). m/z (ES+) 268 (M+1). the mixture was stirred at room temperature for 20 hours extracted with ethyl acetate (2×200 mL) The combined organic fractions were dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (40:60 increasing to 30:70)

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

Procedure: Glyoxal trimeric dihydrate (15.8 g, 75 mmol) was added to a mixture of N-phenylmethyl-N′-(2-pyridinyl)-1,2-ethanediamine (Description 146, 5.7 g, 25 mmol) and hydrochloric acid (2N, 100 mL) and the mixture was stirred at room temperature for 24 hours. Further glyoxal trimeric dihydrate (5.3 g, 25 mmol) was added and the mixture was stirred at room temperature for 20 hours. The mixture was basified with aqueous sodium hydroxide (4M) and extracted with ethyl acetate (2×200 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (40:60 increasing to 30:70), to give the title compound as a light brown oil (3.6 g, 54%). m/z (ES+) 268 (M+1). the mixture was stirred at room temperature for 20 hours extracted with ethyl acetate (2×200 mL) The combined organic fractions were dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (40:60 increasing to 30:70)

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

Procedure: To a solution of [(2R)-7,8-diamino-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (2.226 g, 5.258 mmole) in water (50 mL) was added a solution of glyoxal trimeric dihydrate (1.104 g, 5.258 mmole) in ethyl alcohol (50 mL) and the reaction mixture was heated at 60° C. for 3 hours. The reaction mixture was allowed to cool to room temperature and was diluted with aqueous sodium hydrogen carbonate (250 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water (100 mL), aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 7:3) gave 1.135 g (58%) of the (R)-enantiomer of the title compound as a brown crystalline solid. Rf=0.27 (silica, ethyl acetate:hexanes 3:2); mp 124–127° C. to cool to room temperature extracted with ethyl acetate (2×100 mL) The combined organic extracts were washed with water (100 mL), aqueous sodium chloride (100 mL) dried (magnesium sulfate) the solvent was removed in vacuo to give a crude solid Purification by flash column chromatography (silica, ethyl acetate:hexanes 7:3)

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

Procedure: To a solution of [(2R)-7,8-diamino-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (2.226 g, 5.258 mmole) in water (50 mL) was added a solution of glyoxal trimeric dihydrate (1.104 g, 5.258 mmole) in ethyl alcohol (50 mL) and the reaction mixture was heated at 60° C. for 3 hours. The reaction mixture was allowed to cool to room temperature and was diluted with aqueous sodium hydrogen carbonate (250 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water (100 mL), aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 7:3) gave 1.135 g (58%) of the (R)-enantiomer of the title compound as a brown crystalline solid. Rf=0.27 (silica, ethyl acetate:hexanes 3:2); mp 124-127° C. to cool to room temperature extracted with ethyl acetate (2×100 mL) The combined organic extracts were washed with water (100 mL), aqueous sodium chloride (100 mL) dried (magnesium sulfate) the solvent was removed in vacuo to give a crude solid Purification by flash column chromatography (silica, ethyl acetate:hexanes 7:3)