2-(hydroxymethyl)butane-1,4-diol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an acetone (30 ml) solution of the 2-(hydroxymethyl)butane-1,4-diol (3.4 g, 28.3 mmol) obtained in accordance with the method described in J. Med. Chem., 30 (9), 1636-1642 (1987), p-toluenesulfonic acid monohydrate (244 mg, 2.83 mmol) was added at room temperature and the mixture was stirred for 15 hours. To the reaction mixture, triethylamine (394 μl, 2.83 mmol) was added and the mixture was concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to obtain the title compound (1.0 g, yield: 22%) as a light yellow oil. the mixture was concentrated The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of compound 31 (160 g, 1.30 mol) and 2,2′-dimethoxypropane (207 g, 1.90 mol) in dry acetone (800 mL) was added p-TsOH (9.2 g, 0.053 mol) under N2 and stirred at RT for 12 h. To this was added triethylamine drop-wise to neutral pH and then concentrated under vacuum below 35° C. The crude residue was purified by column chromatography over neutral alumina (12% ethyl acetate in pet. ether) to give the title compound (84 g, 39%). TLC: Pet. ether/EtOAc, 1:1, Rf=0.2 concentrated under vacuum below 35° C The crude residue was purified by column chromatography over neutral alumina (12% ethyl acetate in pet. ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an acetone (30 ml) solution of the 2-(hydroxymethyl)butane-1,4-diol (3.4 g, 28.3 mmol) obtained in accordance with the method described in J. Med. Chem., 30 (9), 1636-1642 (1987), p-toluenesulfonic acid monohydrate (244 mg, 2.83 mmol) was added at room temperature and the mixture was stirred for 15 hours. To the reaction mixture, triethylamine (394 μl, 2.83 mmol) was added and the mixture was concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to obtain the title compound (1.0 g, yield: 22%) as a light yellow oil. the mixture was concentrated The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an acetone (30 ml) solution of the 2-(hydroxymethyl)butane-1,4-diol (3.4 g, 28.3 mmol) obtained in accordance with the method described in J. Med. Chem., 30 (9), 1636-1642 (1987), p-toluenesulfonic acid monohydrate (244 mg, 2.83 mmol) was added at room temperature and the mixture was stirred for 15 hours. To the reaction mixture, triethylamine (394 μl, 2.83 mmol) was added and the mixture was concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to obtain the title compound (1.0 g, yield: 22%) as a light yellow oil. the mixture was concentrated The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of compound 31 (160 g, 1.30 mol) and 2,2′-dimethoxypropane (207 g, 1.90 mol) in dry acetone (800 mL) was added p-TsOH (92 g, 0.053 mol) under N2 and stirred at RT for 12 h. To this was added triethylamine drop-wise to neutral pH and then concentrated under vacuum below 35° C. The crude residue was purified by column chromatography over neutral alumina (12% ethyl acetate in pet ether) to give the title compound (84 g, 39%). TLC: Pet ether/EtOAc, 1:1, Rf=0.2 concentrated under vacuum below 35° C The crude residue was purified by column chromatography over neutral alumina (12% ethyl acetate in pet ether)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an acetone (30 ml) solution of the 2-(hydroxymethyl)butane-1,4-diol (3.4 g, 28.3 mmol) obtained in accordance with the method described in J. Med. Chem., 30 (9), 1636-1642 (1987), p-toluenesulfonic acid monohydrate (244 mg, 2.83 mmol) was added at room temperature and the mixture was stirred for 15 hours. To the reaction mixture, triethylamine (394 μl, 2.83 mmol) was added and the mixture was concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to obtain the title compound (1.0 g, yield: 22%) as a light yellow oil. the mixture was concentrated The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,4-dihydroxy-2-hydroxymethylbutane (12 g, 100 mmol) in tetrahydrofuran (25 ml), 2,2-dimethoxypropane (13.5 g, 110 mmol) and p-toluenesulphonic acid monohydrate (0.57 g, 3 mmol) were added. The solution was stirred for 0.5 hour at room temperature and was then neutralised by addition of triethylamine. The solvent was removed and the residue purified by column chromatography on silica gel eluting with chloroform.-methanol mixtures to afford 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan as a clear colourless liquid (6.5 g, 41%). The solvent was removed the residue purified by column chromatography on silica gel eluting with chloroform

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,4-dihydroxy-2-hydroxymethylbutane (12 g, 100 mmol) in tetrahydrofuran (25 ml), 2,2-dimethoxypropane (13.5 g, 110 mmol) and p-toluenesulphonic acid monohydrate (0.57 g, 3 mmol) were added. The solution was stirred for 0.5 hour at room temperature and was then neutralised by addition of triethylamine. The solvent was removed and the residue purified by column chromatography on silica gel eluting with chloroform-methanol mixtures to afford 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan as a clear colourless liquid (6.5 g, 41%). The solvent was removed the residue purified by column chromatography on silica gel eluting with chloroform-methanol mixtures

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,4-dihydroxy-2-hydroxymethylbutane (12 g, 100 mmol) in tetrahydrofuran (25 ml), 2,2-dimethoxypropane (13.5 g, 110 mmol) and p-toluenesulphonic acid monohydrate (0.57 g, 3 mmol) were added. The solution was stirred for 0.5 hour at room temperature and was then neutralised by addition of triethylamine. The solvent was removed and the residue purified by column chromatography on silica gel eluting with chloroform-methanol mixtures to afford 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan as a clear colourless liquid (6.5 g, 41%). The solvent was removed the residue purified by column chromatography on silica gel eluting with chloroform-methanol mixtures

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of compound 31 (160 g, 1.30 mol) and 2,2′-dimethoxypropane (207 g, 1.90 mol) in dry acetone (800 mL) was added p-TsOH (9.2 g, 0.053 mol) under N2 and stirred at RT for 12 h. To this was added triethylamine drop-wise to neutral pH and then concentrated under vacuum below 35° C. The crude residue was purified by column chromatography over neutral alumina (12% ethyl acetate in pet. ether) to give the title compound (84 g, 39%). TLC: Pet. ether/EtOAc, 1:1, Rf=0.2 concentrated under vacuum below 35° C The crude residue was purified by column chromatography over neutral alumina (12% ethyl acetate in pet. ether)