[(4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.7 mmol of n-butyllithium (1.59 molar in n-hexane, 13.6 ml) were added at -78 C to a solution of (4R,5R)-4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane (3.32 g, 20.5 mmol) in 60 ml of tetrahydrofuran ((4R,5R)-4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane was prepared according to J. Org. Chem. 33 (1968), page 2171). After stirring for 10 minutes, a solution of p-toluenesulfonyl chloride (4 g, 21 mmol) in 20 ml of tetrahydrofuran which was cooled to −78° C. was added. After stirring at −78° C. for 15 minutes, the mixture was warmed to 20° C. and poured into 200 ml of concentrated sodium chloride solution. The organic phase was separated off and the aqueous phase was extracted twice with 50 ml of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on 400 g of silica gel using ethyl acetate and n-hexane in the weight ratio 60:40 as eluent. 74.6% of (4R,5R)-[5-hydroxymethyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl p-toluenesulfonate were obtained ([α]D19=+11.80 (c=1.88 in trichloromethane); cf. J. Org. Chem. 55 (1990), page 4417: [α]D21=+11.30 (c=2.70 in trichloromethane)). was added After stirring at −78° C. for 15 minutes The organic phase was separated off the aqueous phase was extracted twice with 50 ml of ethyl acetate The combined organic phases were dried over anhydrous sodium sulfate concentrated The residue was chromatographed on 400 g of silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.7 mmol of n-butyllithium (1.59 molar in n-hexane, 13.6 ml) were added at -78 C to a solution of (4R,5R)-4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane (3.32 g, 20.5 mmol) in 60 ml of tetrahydrofuran ((4R,5R)-4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane was prepared according to J. Org. Chem. 33 (1968), page 2171). After stirring for 10 minutes, a solution of p-toluenesulfonyl chloride (4 g, 21 mmol) in 20 ml of tetrahydrofuran which was cooled to −78° C. was added. After stirring at −78° C. for 15 minutes, the mixture was warmed to 20° C. and poured into 200 ml of concentrated sodium chloride solution. The organic phase was separated off and the aqueous phase was extracted twice with 50 ml of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on 400 g of silica gel using ethyl acetate and n-hexane in the weight ratio 60:40 as eluent. 74.6% of (4R,5R)-[5-hydroxymethyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl p-toluenesulfonate were obtained ([α]D19=+11.80 (c=1.88 in trichloromethane); cf. J. Org. Chem. 55 (1990), page 4417: [α]D21=+11.30 (c=2.70 in trichloromethane)). was added After stirring at −78° C. for 15 minutes The organic phase was separated off the aqueous phase was extracted twice with 50 ml of ethyl acetate The combined organic phases were dried over anhydrous sodium sulfate concentrated The residue was chromatographed on 400 g of silica gel

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

Procedure: To THF (50 mL), NaH (1.41 g, 0.032 mmol) was added at room temperature, followed by addition of ((4R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (5.0 g, 0.031 mmol) at room temperature. The mixture was stirred at room temperature for 1 hr. After that, TBSCl (5.11 g, 0.034 mmol) was added at room temperature and stirred at room temperature overnight. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (8.21 g, 96%). stirred at room temperature overnight extracted with ethyl acetate The organic layer was dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane)

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

Procedure: To THF (50 mL), NaH (1.41 g, 0.032 mmol) was added at room temperature, followed by addition of ((4R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (5.0 g, 0.031 mmol) at room temperature. The mixture was stirred at room temperature for 1 hr. After that, TBSCl (5.11 g, 0.034 mmol) was added at room temperature and stirred at room temperature overnight. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (8.21 g, 96%). stirred at room temperature overnight extracted with ethyl acetate The organic layer was dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane)

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

Procedure: A solution of (4R-trans)-(-)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (51 g) in THF (400 ml) was added dropwise to a stirred suspension of sodium hydride (17.5 g of 80% in oil) in THF (200 ml). After 0.75 h, benzyl bromide (116.3 g) was added dropwise and the resulting mixture was stirred for 18 h, and was then heated at reflux for 2 h. After stirring for a further 20 h at 20°, the mixture was cooled in ice, water (10 ml) was added and the mixture was evaporated to dryness. The residue was extracted with ER, and the organic solution was dried and the solvent was evaporated giving a crude product (130 g) which was used without further purification. was then heated at reflux for 2 h After stirring for a further 20 h at 20° the mixture was cooled in ice the mixture was evaporated to dryness The residue was extracted with ER the organic solution was dried the solvent was evaporated

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

Procedure: To THF (50 mL), NaH (1.41 g, 0.032 mmol) was added at room temperature, followed by addition of ((4R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (5.0 g, 0.031 mmol) at room temperature. The mixture was stirred at room temperature for 1 hr. After that, TBSCl (5.11 g, 0.034 mmol) was added at room temperature and stirred at room temperature overnight. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (8.21 g, 96%). stirred at room temperature overnight extracted with ethyl acetate The organic layer was dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane)

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

Procedure: The starting material (1) (3,4-O-isopropylidene-D-mannitol) was reacted with sodium periodate and potassium borohydride as described in J. Chem. Soc., Perkin Trans. I., 1972, 275 (the contents of which are herein incorporated by reference) to yield compound (2) in 92% yield. Compound (2) (5.1 g) was dissolved in pyridine (40 ml) and cooled in ice. To this solution was added methanesulphonyl chloride (18 ml), dropwise with stirring. The mixture was allowed to stand at room temperature for 3 hours, after which time it was added to a solution of sodium bicarbonate. This solution was then extracted with dichloromethane (5×50 ml) and the combined extracts were dried (MgSO4) and concentrated in vacuo. The residue obtained was recrystallised from ethanol to give 2,3-O-isopropylidene-1,4-di-O-methanesulphonyl-D-threitol (3), (6.6 g, 66%), m.p. 83°-85° C. cooled in ice This solution was then extracted with dichloromethane (5×50 ml) the combined extracts were dried (MgSO4) concentrated in vacuo The residue obtained was recrystallised from ethanol

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

Procedure: The starting material (1) (3,4-O-isopropylidene-D-mannitol) was reacted with sodium periodate and potassium borohydride as described in J. Chem. Soc., Perkin Trans. I., 1972, 275 (the contents of which are herein incorporated by reference) to yield compound (2) in 92% yield. Compound (2) (5.1 g) was dissolved in pyridine (40 ml) and cooled in ice. To this solution was added methanesulphonyl chloride (18 ml), dropwise with stirring. The mixture was allowed to stand at room temperature for 3 hours, after which time it was added to a solution of sodium bicarbonate. This solution was then extracted with dichloromethane (5×50 ml) and the combined extracts were dried (MgSO4) and concentrated in vacuo. The residue obtained was recrystallised from ethanol to give 2,3-O-isopropylidene-1,4-di-O-methanesulphonyl-D-threitol (3), (6.6 g, 66%), m.p. 83°-85° C. cooled in ice This solution was then extracted with dichloromethane (5×50 ml) the combined extracts were dried (MgSO4) concentrated in vacuo The residue obtained was recrystallised from ethanol

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

Procedure: The starting material (1) (3,4-O-isopropylidene-D-mannitol) was reacted with sodium periodate and potassium borohydride as described in J. Chem. Soc., Perkin Trans. I., 1972, 275 (the contents of which are herein incorporated by reference) to yield compound (2) in 92% yield. Compound (2) (5.1 g) was dissolved in pyridine (40 ml) and cooled in ice. To this solution was added methanesulphonyl chloride (18 ml), dropwise with stirring. The mixture was allowed to stand at room temperature for 3 hours, after which time it was added to a solution of sodium bicarbonate. This solution was then extracted with dichloromethane (5×50 ml) and the combined extracts were dried (MgSO4) and concentrated in vacuo. The residue obtained was recrystallised from ethanol to give 2,3-O-isopropylidene-1,4-di-O-methanesulphonyl-D-threitol (3), (6.6 g, 66%), m.p. 83°-85° C.

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

Procedure: Such a reaction sequence is illustrated for R=methyl by way of example in Scheme 1, for the preparation of the (4R, 5R)-compound. The starting material, the known 3,4-O-isopropylidene-D-mannitol (1), is reacted with periodate ion, and the product of glycol cleavage is reduced with sodium borohydride to afford 2,3-O-isopropylidene-D-threitol (2). Sulphonylation of (2) with methanesulphonyl chloride affords the di-methanesulphonate (3), which undergoes displacement with azide ion to yield the diazide(4). Catalytic reduction of (4) gives the (4R,5R)-diamine (5), which is reacted, generally without isolation, with potassium tetrachloroplatinate, to afford (4R,5R)-(I).

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

Procedure: Such a reaction sequence is illustrated for R=methyl by way of example in Scheme 1, for the preparation of the (4R, 5R)-compound. The starting material, the known 3,4-O-isopropylidene-D-mannitol (1), is reacted with periodate ion, and the product of glycol cleavage is reduced with sodium borohydride to afford 2,3-O-isopropylidene-D-threitol (2). Sulphonylation of (2) with methanesulphonyl chloride affords the di-methanesulphonate (3), which undergoes displacement with azide ion to yield the diazide(4). Catalytic reduction of (4) gives the (4R,5R)-diamine (5), which is reacted, generally without isolation, with potassium tetrachloroplatinate, to afford (4R,5R)-(I).

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.7 mmol of n-butyllithium (1.59 molar in n-hexane, 13.6 ml) were added at -78 C to a solution of (4R,5R)-4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane (3.32 g, 20.5 mmol) in 60 ml of tetrahydrofuran ((4R,5R)-4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane was prepared according to J. Org. Chem. 33 (1968), page 2171). After stirring for 10 minutes, a solution of p-toluenesulfonyl chloride (4 g, 21 mmol) in 20 ml of tetrahydrofuran which was cooled to −78° C. was added. After stirring at −78° C. for 15 minutes, the mixture was warmed to 20° C. and poured into 200 ml of concentrated sodium chloride solution. The organic phase was separated off and the aqueous phase was extracted twice with 50 ml of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on 400 g of silica gel using ethyl acetate and n-hexane in the weight ratio 60:40 as eluent. 74.6% of (4R,5R)-[5-hydroxymethyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl p-toluenesulfonate were obtained ([α]D19=+11.80 (c=1.88 in trichloromethane); cf. J. Org. Chem. 55 (1990), page 4417: [α]D21=+11.30 (c=2.70 in trichloromethane)). was added After stirring at −78° C. for 15 minutes The organic phase was separated off the aqueous phase was extracted twice with 50 ml of ethyl acetate The combined organic phases were dried over anhydrous sodium sulfate concentrated The residue was chromatographed on 400 g of silica gel