2-(2,2-dimethyl-1,3-dioxan-5-yl)ethanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of compound 32 (84 g, 0.528 mol) in dry DMF (500 mL) was added triphenylphosphine (207 g, 0.79 mol) with vigorous stirring until it becomes a clear solution. The mixture was cooled to 0° C. and added CBr4 (260 g, 0.79 mol) portion wise over a period of 30 min and allowed to stir at RT for 5 h. The reaction mixture was cooled to 0° C., added saturated NaHCO3 solution (200 mL) and extracted with hexane (4×200 mL). The combined organic layer was dried, concentrated under vacuum and the crude title compound (117 g) was used for next reaction without any purification. TLC: Pet. ether/EtOAc, 7:3, Rf=0.6 to stir at RT for 5 h The reaction mixture was cooled to 0° C. extracted with hexane (4×200 mL) The combined organic layer was dried concentrated under vacuum the crude title compound (117 g) was used for next reaction without any purification

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

Procedure: 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)

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

Procedure: The same procedure as in the steps (6b) to (6f) of Example 6 was repeated using 2-(2,2-dimethyl-1,3-dioxan-5-yl)ethanol obtained in the step (28a) to obtain the title compound (58 mg, total yield: 2.0%) as a light yellow solid. obtained in the step (28a)

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

Procedure: 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)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The same procedure as in the steps (6b) to (6f) of Example 6 was repeated using 2-(2,2-dimethyl-1,3-dioxan-5-yl)ethanol obtained in the step (28a) to obtain the title compound (58 mg, total yield: 2.0%) as a light yellow solid. obtained in the step (28a)

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

Procedure: 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)

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

Procedure: To a solution of compound 32 (84 g, 0.528 mol) in dry DMF (500 mL) was added triphenylphosphine (207 g, 0.79 mol) with vigorous stirring until it becomes a clear solution. The mature was cooled to 0° C. and added CBr4 (260 g, 0.79 mol) portion wise over a period of 30 min and allowed to stir at RT for 5 h. The reaction mixture was cooled to 0° C., added saturated NaHCO3 solution (200 mL) and extracted with hexane (4×200 mL). The combined organic layer was dried, concentrated under vacuum and the crude title compound (117 g) was used for next reaction without any purification. TLC: Pet. ether/EtOAc, 7:3, Rf=0.6 to stir at RT for 5 h The reaction mixture was cooled to 0° C. extracted with hexane (4×200 mL) The combined organic layer was dried concentrated under vacuum the crude title compound (117 g) was used for next reaction without any purification

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

Procedure: 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)