2-(oxolan-2-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:0.00; pressure:0.00; stir:

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

Procedure: A mixture of ethyl 4-methyl-2-(4-pyridyl)thiazole-5-carboxylate (744 mg), 1 N NaOH (4 ml) and tetrahydrofuran-ethanol (1:1, 6 ml) was stirred at room temperature for 1 hour and diluted with water, to which was added 1 N hydrochloric acid (4 ml) to give the title compound as crystals (595 mg, 90.2%).

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

Procedure: A mixture of ethyl 4-methyl-2-(4-pyridyl)thiazole-5-carboxylate (744 mg), 1 N NaOH (4 ml) and tetrahydrofuran-ethanol (1:1, 6 ml) was stirred at room temperature for 1 hour and diluted with water, to which was added 1 N hydrochloric acid (4 ml) to give the title compound as crystals (595 mg, 90.2%).

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

Procedure: To an ice cooled stirring solution of 2-(tetrahydrofuran-2-yl)ethanol (1.9 g) and triethylamine (4.4 ml) in dry dichloromethane (30 ml) was added dropwise over 5 min methanesulphonyl chloride (1.59 ml). The mixture was allowed to warm slowly to ambient temperature over 16 h then washed with saturated sodium hydrogen carbonate. The aqueous layer was further extracted with dichloromethane and the combined extracts washed with brine, dried by passing through a phase separation cartridge and stripped to give the title compound as a light brown oil, yield 3.1 g. then washed with saturated sodium hydrogen carbonate The aqueous layer was further extracted with dichloromethane the combined extracts washed with brine dried by passing through a phase separation cartridge

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

Procedure: To an ice cooled stirring solution of 2-(tetrahydrofuran-2-yl)ethanol (1.9 g) and triethylamine (4.4 ml) in dry dichloromethane (30 ml) was added dropwise over 5 min methanesulphonyl chloride (1.59 ml). The mixture was allowed to warm slowly to ambient temperature over 16 h then washed with saturated sodium hydrogen carbonate. The aqueous layer was further extracted with dichloromethane and the combined extracts washed with brine, dried by passing through a phase separation cartridge and stripped to give the title compound as a light brown oil, yield 3.1 g. then washed with saturated sodium hydrogen carbonate The aqueous layer was further extracted with dichloromethane the combined extracts washed with brine dried by passing through a phase separation cartridge

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

Procedure: To a solution of calcium chloride (540 mg) in a mixed solvent of tetrahydrofuran-ethanol (v/v=1/1, 5.0 mL) was added sodium borohydride (240 mg), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of ethyl 2-(4-((4-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanoate (1.0 g) obtained in Step D of Example 347 in a mixed solvent of tetrahydrofuran-ethanol (v/v=1/1, 5.0 mL) in an ice bath, and the mixture was stirred overnight while it was allowed to be gradually warmed to room temperature. To the reaction mixture was added 1 M hydrochloric acid in an ice bath, and the mixture was stirred at the same temperature for 10 min. 1 M Aqueous sodium hydroxide solution was added thereto, and the solvent was evaporated under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (700 mg). the mixture was stirred overnight while it to be gradually warmed to room temperature the mixture was stirred at the same temperature for 10 min the solvent was evaporated under reduced pressure To the residue was added water the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: To a solution of calcium chloride (540 mg) in a mixed solvent of tetrahydrofuran-ethanol (v/v=1/1, 5.0 mL) was added sodium borohydride (240 mg), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of ethyl 2-(4-((4-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanoate (1.0 g) obtained in Step D of Example 347 in a mixed solvent of tetrahydrofuran-ethanol (v/v=1/1, 5.0 mL) in an ice bath, and the mixture was stirred overnight while it was allowed to be gradually warmed to room temperature. To the reaction mixture was added 1 M hydrochloric acid in an ice bath, and the mixture was stirred at the same temperature for 10 min. 1 M Aqueous sodium hydroxide solution was added thereto, and the solvent was evaporated under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (700 mg). the mixture was stirred overnight while it to be gradually warmed to room temperature the mixture was stirred at the same temperature for 10 min the solvent was evaporated under reduced pressure To the residue was added water the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: A solution of 8.3 g. (0.05 mole) of α-(1-amino-1-methylethyl)benzenemethanol, 9.8 g. (0.05 mole) of 3,4-dimethoxyphenylacetic acid and 13.6 g. (0.055 mole) of EEDQ (Aldrich Chem. Co.) in 300 ml. of tetrahydrofuran-ethanol is refluxed for 45 minutes and then allowed to stand for 20 hours at 25° C. The solution is evaporated in vacuo. The residue is taken up with 250 ml. of ethyl acetate, washed with dilute HCl, followed by washing with aqueous NaHCO3. Subsequently, the extract is washed with aqueous NaCl, dried (Na2SO4) and evaporated to dryness in vacuo. Crystallization of the residue from ether gives 14.0 g. (82% yield) of pure 2-(3,4-dimethoxyphenyl)-N-(β-hydroxy-α,α-dimethylphenethyl)acetamide, m.p. 123°-124° C. The solution is evaporated in vacuo of ethyl acetate, washed with dilute HCl by washing with aqueous NaHCO3 Subsequently, the extract is washed with aqueous NaCl dried (Na2SO4) evaporated to dryness in vacuo Crystallization of the residue from ether gives 14.0 g

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

Procedure: A solution of 8.3 g. (0.05 mole) of α-(1-amino-1-methylethyl)benzenemethanol, 9.8 g. (0.05 mole) of 3,4-dimethoxyphenylacetic acid and 13.6 g. (0.055 mole) of EEDQ (Aldrich Chem. Co.) in 300 ml. of tetrahydrofuran-ethanol is refluxed for 45 minutes and then allowed to stand for 20 hours at 25° C. The solution is evaporated in vacuo. The residue is taken up with 250 ml. of ethyl acetate, washed with dilute HCl, followed by washing with aqueous NaHCO3. Subsequently, the extract is washed with aqueous NaCl, dried (Na2SO4) and evaporated to dryness in vacuo. Crystallization of the residue from ether gives 14.0 g. (82% yield) of pure 2-(3,4-dimethoxyphenyl)-N-(β-hydroxy-α,α-dimethylphenethyl)acetamide, m.p. 123°-124° C. The solution is evaporated in vacuo of ethyl acetate, washed with dilute HCl by washing with aqueous NaHCO3 Subsequently, the extract is washed with aqueous NaCl dried (Na2SO4) evaporated to dryness in vacuo Crystallization of the residue from ether gives 14.0 g