1-(2-bromophenyl)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:

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

Procedure: 17.2 g of o-[tri(cyclohexyl)]tin]benzylalcohol was obtained in the same manner as in the synthesis of tricyclohexyl[o-(1-hydroxyethyl)phenyl]tin of Example 1-(4), with the exception that 9.40 g of o-bromobenzylalcohol (50.2 mmol), prepared in the aforementioned example (1), instead of o-bromo-1-phenyl ethanol (yield=75.1%).

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.1 g of o-bromo-1-phenylethanol (50.2 mmol) and 50 ml of diethylether were mixed together in a 500 ml two-neck flask, which was equipped with a stirrer and isobaric dropping funnel. To this mixture, 64.5 ml of hexane solution of n-butyl lithium was gradually added dropwise at -78° C. Subsequently, the temperature was raised to -30° C., and the mixture was stirred for 1 hour while maintaining the same temperature. The reaction mixture was cooled back to -78° C., and a mixed solvent solution containing 20.2 g of tricyclohexyltin chloride (50.1 mmol), 100 ml of hexane, and 50 ml of diethylether was added dropwise thereto. The temperature was raised back to -30° C., and the mixture was stirred for 12 hours at the same temperature. Upon completion of the reaction, 100 ml of water was added, and the organic substance was extracted three times, with 200 ml of diethylether for each. After the solvent was removed under reduced pressure, the oily product was purified by column chromatography on silica gel (for which, 50 g of silica gel, and a mixed solvent of hexane and diethylether, as a developing solvent, were employed) to yield 17.9 g of the final product (yield=73.0%). which was equipped with a stirrer while maintaining the same temperature The reaction mixture was cooled back to -78° C. was added dropwise The temperature was raised back to -30° C. the mixture was stirred for 12 hours at the same temperature was added the organic substance was extracted three times After the solvent was removed under reduced pressure the oily product was purified by column chromatography on silica gel (for which, 50 g of silica gel

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

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

Procedure: To a stirred solution of 1-(2-bromophenyl)ethanol (step 1, 5.4 g, 25.1 mmol) in tetrahydrofuran (25 mL) was added dropwise a 1.59 M solution of butyllithium in tetrahydrofuran (33 mL, 51.5 mmol) at −78° C. for 20 min and the mixture was stirred for 2 h at the same temperature. To the mixture was added dropwise a solution of ethyl 4-oxopiperidine-1-carboxylate (4.73 g, 27.6 mmol) in tetrahydrofuran (10 mL) at −78° C. for 15 min. This resulting mixture was slowly warmed up to room temperature and stirred for 19 h at the same temperature. The reaction mixture was quenched by the addition of saturated ammonium chloride aqueous solution, and then the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (2/1), then hexane/ethyl acetate (1/1) to afford 1.37 g (19%) of the title compound as a slight yellow syrup: stirred for 19 h at the same temperature The reaction mixture was quenched by the addition of saturated ammonium chloride aqueous solution the organic layer washed with brine dried over sodium sulfate evaporated The residue was purified by column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (2/1)

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

Procedure: To a stirred solution of 1-(2-bromophenyl)ethanol (step 1, 5.4 g, 25.1 mmol) in tetrahydrofuran (25 mL) was added dropwise a 1.59 M solution of butyllithium in tetrahydrofuran (33 mL, 51.5 mmol) at −78° C. for 20 min and the mixture was stirred for 2 h at the same temperature. To the mixture was added dropwise a solution of ethyl 4-oxopiperidine-1-carboxylate (4.73 g, 27.6 mmol) in tetrahydrofuran (10 mL) at −78° C. for 15 min. This resulting mixture was slowly warmed up to room temperature and stirred for 19 h at the same temperature. The reaction mixture was quenched by the addition of saturated ammonium chloride aqueous solution, and then the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (2/1), then hexane/ethyl acetate (1/1) to afford 1.37 g (19%) of the title compound as a slight yellow syrup: stirred for 19 h at the same temperature The reaction mixture was quenched by the addition of saturated ammonium chloride aqueous solution the organic layer washed with brine dried over sodium sulfate evaporated The residue was purified by column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (2/1)

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

Procedure: To a stirred solution of 1-(2-bromophenyl)ethanone (5 g, 25.1 mmol) in methanol (50 mL) was added sodium borohydride (1.43 g, 37.7 mmol) at room temperature and the mixture was stirred for 24 h at the same temperature. The reaction mixture was quenched by the addition of water, and concentrated to give a colorless residue. The crude material was partitioned between diethyl ether and water, and then the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/ethyl acetate (5/1) to afford 5.4 g (quant.) of the title compound as a colorless oil: The reaction mixture was quenched by the addition of water concentrated to give a colorless residue The crude material was partitioned between diethyl ether and water the organic layer washed with brine dried over sodium sulfate evaporated The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/ethyl acetate (5/1)

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

Procedure: 2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (139 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-bromo-α-methylbenzyl alcohol (90 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 33%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column