2-(oxan-4-yloxy)ethanol

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

Procedure: Into a 50-mL 3-necked round-bottom flask, was placed FeCl3 (800 mg, 4.94 mmol, 0.10 equiv). This was followed by the addition of oxan-4-ol (5 g, 48.96 mmol, 1.00 equiv) at 0° C. To this was added oxirane (20 mL) dropwise with stirring at 0° C. The resulting solution was stirred overnight at room temperature. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×50 mL of ethyl acetate and the organic layers combined. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:30-1:1). Purification afforded 2.25 g (crude) of 2-(oxan-4-yloxy)ethan-1-ol (54.2) as a colorless oil. Into a 50-mL 3-necked round-bottom flask, was placed The resulting solution was stirred overnight at room temperature The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 2×50 mL of ethyl acetate Purification

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,4,8-Trioxaspiro[4.5]decane (0.43 g, 3.0 mmol) produced in Reference Example 13 (13a) was dissolved in tetrahydrofuran (1.0 mL), and the resulting mixture was cooled to −50° C. Subsequently, a 1.0M solution of borane-tetrahydrofuran complex in tetrahydrofuran (3.6 mL) and trimethylsilyl trifluoromethanesulfonate (33 mg, 0.15 mmol) were added. The resulting mixture was warmed to room temperature, followed by stirring for 18 hours. A small amount of water was added, and then the resulting mixture was purified by basic silica gel column chromatography (hexane:ethyl acetate, 100:0-0:100, V/V) to give the desired title compound (0.39 g, yield 88%). The resulting mixture was warmed to room temperature the resulting mixture was purified by basic silica gel column chromatography (hexane:ethyl acetate, 100:0-0:100, V/V)

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

Procedure: To a suspension of 4-chloro-6-cyano-7-hydroxyquinoline (400 mg, 1.95 mmol), (prepared as described for the starting material in Example 1), 4-(2-hydroxyethoxy)tetrahydropyran (371 mg, 2.54 mmol) and triphenylphosphine (820 mg, 3.12 mmol) in methylene choride (15 ml) was added diethyl azodicarboxylate (492 μl, 3.12 mmol) in portions. After stirring for 30 minutes, triphenylphosphine (512 mg, 1.95 mmol), 4-(2-hydroxyethoxy)-tetrahydropyran (142 mg, 0.98 mmol) and diethyl azodicarboxylate (308 μl, 1.95 mmol) were added. The volatiles were removed under vacuum and the residue was purified by column chrolatography eluting with methylene chloride/ethyl actetate/methanol (60/40/0 followed by 50/50/0, 40/60/0, 60/39/1, 60/38/2 and 50/46/4) to give 4-chloro-6-cyano-7-(2-(tetrahydropyran-4-yloxy)ethoxy)quinoline (519 mg, 65%). (prepared The volatiles were removed under vacuum the residue was purified by column chrolatography eluting with methylene chloride/ethyl

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

Procedure: Into a 50-mL 3-necked round-bottom flask, was placed FeCl3 (800 mg, 4.94 mmol, 0.10 equiv). This was followed by the addition of oxan-4-ol (5 g, 48.96 mmol, 1.00 equiv) at 0° C. To this was added oxirane (20 mL) dropwise with stirring at 0° C. The resulting solution was stirred overnight at room temperature. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×50 mL of ethyl acetate and the organic layers combined. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:30-1:1). Purification afforded 2.25 g (crude) of 2-(oxan-4-yloxy)ethan-1-ol (54.2) as a colorless oil. Into a 50-mL 3-necked round-bottom flask, was placed The resulting solution was stirred overnight at room temperature The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 2×50 mL of ethyl acetate Purification