(3S,4S)-oxolane-3,4-diol

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

Procedure: A mixture of (3S,4S)-tetrahydrofuran-3,4-diol (9.35 g, 89.8 mmol), t-butyldimethylchlorosilane (14.9 g, 98.8 mmol), TEA (13.8 mL, 98.8 mmol), and dichloromethane (100 mL) is stirred at room temperature for 4 days. The reaction is concentrated in vacuo and purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining) to give 3.66 g (19%) of the title compound as a light yellow oil. GC-MS m/z 161 (M-tBu)+. The reaction is concentrated in vacuo purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining)

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

Procedure: A mixture of (3S,4S)-tetrahydrofuran-3,4-diol (9.35 g, 89.8 mmol), t-butyldimethylchlorosilane (14.9 g, 98.8 mmol), TEA (13.8 mL, 98.8 mmol), and dichloromethane (100 mL) is stirred at room temperature for 4 days. The reaction is concentrated in vacuo and purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining) to give 3.66 g (19%) of the title compound as a light yellow oil. GC-MS m/z 161 (M-tBu)+. The reaction is concentrated in vacuo purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining)

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

Procedure: A mixture of (3S,4S)-tetrahydrofuran-3,4-diol (9.35 g, 89.8 mmol), t-butyldimethylchlorosilane (14.9 g, 98.8 mmol), TEA (13.8 mL, 98.8 mmol), and dichloromethane (100 mL) is stirred at room temperature for 4 days. The reaction is concentrated in vacuo and purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining) to give 3.66 g (19%) of the title compound as a light yellow oil. GC-MS m/z 161 (M-tBu)+. The reaction is concentrated in vacuo purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining)

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

Procedure: To a solution of 1,4-anhydro-D-threitol [prepared from D-threiol (manufactured by Fluka Co.) in the same manner as in the preparation of 1,4-anhydro-L-threitol (cf. J. Am. Chem. Soc., 74, 5336 (1952)] (11.43 g) and 2,4-dichloroquinazoline (16.8 g) in dimethylformamide (78 ml) is added gradually 60% sodium hydride (in oil) (4.39 g) with stirring under ice-cooling, and the mixture is stirred under ice-cooling for 15 minutes and further at room temperature for 30 minutes. The reaction mixture is diluted with ethyl acetate and washed with water 5 times. The ethyl acetate solution is dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. The resulting residue is briefly purified by medium pressure liquid column chromatography [eluent, chloroform] to give a crystalline substance. The crystalline substance is dividedly added to a solution of piperazine (20.7 g) in dioxane (95 ml) with stirring at 55° C., and the mixture is stirred at the same temperature for 30 minutes. The reaction mixture is diluted with ethyl acetate, washed with water, and dried over anhydrous magnesium sulfate. The resulting solution is evaporated to dryness under reduced pressure, and the residue is purified by medium pressure column chromatography (eluent, chloroform:methanol=10:1, 5:1, v/v) to give 4-[(3R,4R)-(4-hydroxytetrahydrofuran-3-yl)oxy]-2-(1-piperazinyl)quinazoline (5.83 g) as crystals. A part thereof is crystallized from ethanol-ether for obtaining the following physical data. cooling the mixture is stirred under ice- washed with water 5 times The ethyl acetate solution is dried over anhydrous magnesium sulfate evaporated to dryness under reduced pressure The resulting residue is briefly purified by medium pressure liquid column chromatography [eluent, chloroform] to give a crystalline substance with stirring at 55° C. the mixture is stirred at the same temperature for 30 minutes washed with water dried over anhydrous magnesium sulfate The resulting solution is evaporated to dryness under reduced pressure the residue is purified by medium pressure column chromatography (eluent, chloroform

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

Procedure: To a solution of 1,4-anhydro-L-threitol [manufactured by Aldrich Co., cf. J. Am. Chem. Soc., 74, 5336 (1952)] (7.34 g) and 2,4-dichloroquinazoline (5.00 g) in dimethylformamide (42 ml) is added gradually 60% sodium hydride (in oil) (1.92 g) with stirring under ice-cooling, and the mixture is stirred at room temperature for one hour and 10 minutes. The reaction mixture is diluted with ethyl acetate and washed with water 5 times. The ethyl acetate solution is dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. The resulting residue is briefly purified by medium pressure liquid column chromatography [eluent, chloroform, (chloroform:methanol=200:1, v/v) ] to give an oily substance. The oily substance is dissolved in dioxane (35 ml), and the mixture is slowly added dropwise to a solution of piperazine (9.61 g) in dioxane (70 ml) with stirring at 50° C., and the mixture is stirred at the same temperature for 1.5 hour. The reaction mixture is diluted with ethyl acetate, washed with water, and dried over anhydrous magnesium sulfate. The resulting solution is evaporated to dryness under reduced pressure, and the residue is purified by medium pressure column chromatography (eluent, chloroform:methanol=10:1, 5:1, v/v) to give 4-[(3S,4S)-(4-hydroxytetrahydrofuran-3-yl)oxy]-2-(1-piperazinyl)quinazoline (2.47 g) as crystals. cooling the mixture is stirred at room temperature for one hour and 10 minutes washed with water 5 times The ethyl acetate solution is dried over anhydrous magnesium sulfate evaporated to dryness under reduced pressure The resulting residue is briefly purified by medium pressure liquid column chromatography [eluent, chloroform (chloroform:methanol=200:1, v/v) ] to give an oily substance with stirring at 50° C. the mixture is stirred at the same temperature for 1.5 hour washed with water dried over anhydrous magnesium sulfate The resulting solution is evaporated to dryness under reduced pressure the residue is purified by medium pressure column chromatography (eluent, chloroform

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

Procedure: A mixture of (3S,4S)-tetrahydrofuran-3,4-diol (9.35 g, 89.8 mmol), t-butyldimethylchlorosilane (14.9 g, 98.8 mmol), TEA (13.8 mL, 98.8 mmol), and dichloromethane (100 mL) is stirred at room temperature for 4 days. The reaction is concentrated in vacuo and purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining) to give 3.66 g (19%) of the title compound as a light yellow oil. GC-MS m/z 161 (M-tBu)+. The reaction is concentrated in vacuo purified on silica gel (330 g, 35-80% EtOAc/hexanes, observed on TLC using KMnO4 staining)