4-bromo-2-methoxy-1-phenylmethoxybenzene

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: 25 ml of tert.-butyllithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 10 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 100 ml of tetrahydrofuran. After stirring at -70° for 1 hour, 5 g of quinoline-4-carbaldehyde dissolved in 50 ml of tetrahydrofuran are added dropwise within 30 minutes. The reaction mixture is stirred at -40° for 1 hour and at -5° for 1 hour, poured into 200 ml of water and adjusted to pH 4 with glacial acetic acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with water, dried over sodium sulfate and evaporated. There is obtained α-[4-(benzyloxy)-3-methoxyphenyl]-4-quinolinemethanol as an amorphous solid. are added dropwise within 30 minutes The reaction mixture is stirred at -40° for 1 hour and at -5° for 1 hour The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with water dried over sodium sulfate evaporated

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

Procedure: 25 ml of tert.-butyllithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 10 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 100 ml of tetrahydrofuran. After stirring at -70° for 1 hour, 5 g of quinoline-4-carbaldehyde dissolved in 50 ml of tetrahydrofuran are added dropwise within 30 minutes. The reaction mixture is stirred at -40° for 1 hour and at -5° for 1 hour, poured into 200 ml of water and adjusted to pH 4 with glacial acetic acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with water, dried over sodium sulfate and evaporated. There is obtained α-[4-(benzyloxy)-3-methoxyphenyl]-4-quinolinemethanol as an amorphous solid. are added dropwise within 30 minutes The reaction mixture is stirred at -40° for 1 hour and at -5° for 1 hour The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with water dried over sodium sulfate evaporated

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

Procedure: aa) 10 ml of tert.butyl lithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 4.1 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 40 ml of tetrahydrofuran. After stirring at -70° for 2 hours. 1 ml of pyridine-3-carbaldehyde is added within 5 minutes. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours, and poured into 100 ml of 1N hydrochloric acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water. The combined aqueous phases are made alkaline with aqueous ammonia solution and extracted three times with 100 ml of methylene chloride each time. The combined methylene chloride phases are dried over sodium sulfate and evaporated. There is obtained alpha-[4-(benzyloxy)-3 -methoxyphenyl]-3-pyridinemethanol as an oil. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water extracted three times with 100 ml of methylene chloride each time The combined methylene chloride phases are dried over sodium sulfate evaporated

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

Procedure: aa) 10 ml of tert.butyl lithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 4.1 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 40 ml of tetrahydrofuran. After stirring at -70° for 2 hours. 1 ml of pyridine-3-carbaldehyde is added within 5 minutes. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours, and poured into 100 ml of 1N hydrochloric acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water. The combined aqueous phases are made alkaline with aqueous ammonia solution and extracted three times with 100 ml of methylene chloride each time. The combined methylene chloride phases are dried over sodium sulfate and evaporated. There is obtained alpha-[4-(benzyloxy)-3 -methoxyphenyl]-3-pyridinemethanol as an oil. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water extracted three times with 100 ml of methylene chloride each time The combined methylene chloride phases are dried over sodium sulfate evaporated

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

Procedure: 25 ml of tert.-butyllithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 10 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 100 ml of tetrahydrofuran. After stirring at -70° for 1 hour, 5 g of quinoline-4-carbaldehyde dissolved in 50 ml of tetrahydrofuran are added dropwise within 30 minutes. The reaction mixture is stirred at -40° for 1 hour and at -5° for 1 hour, poured into 200 ml of water and adjusted to pH 4 with glacial acetic acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with water, dried over sodium sulfate and evaporated. There is obtained α-[4-(benzyloxy)-3-methoxyphenyl]-4-quinolinemethanol as an amorphous solid. are added dropwise within 30 minutes The reaction mixture is stirred at -40° for 1 hour and at -5° for 1 hour The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with water dried over sodium sulfate evaporated

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

Procedure: aa) 10 ml of tert.butyl lithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 4.1 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 40 ml of tetrahydrofuran. After stirring at -70° for 2 hours. 1 ml of pyridine-3-carbaldehyde is added within 5 minutes. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours, and poured into 100 ml of 1N hydrochloric acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water. The combined aqueous phases are made alkaline with aqueous ammonia solution and extracted three times with 100 ml of methylene chloride each time. The combined methylene chloride phases are dried over sodium sulfate and evaporated. There is obtained alpha-[4-(benzyloxy)-3-methoxyphenyl]-3-pyridinemethanol as an oil. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water extracted three times with 100 ml of methylene chloride each time The combined methylene chloride phases are dried over sodium sulfate evaporated

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

Procedure: aa) 10 ml of tert.butyl lithium solution (1.4M in hexane) are added dropwise at -70° within 10 minutes to 4.1 g of 4-(benzyloxy)-3-methoxy-bromobenzene dissolved in 40 ml of tetrahydrofuran. After stirring at -70° for 2 hours. 1 ml of pyridine-3-carbaldehyde is added within 5 minutes. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours, and poured into 100 ml of 1N hydrochloric acid. The mixture is extracted three times with 50 ml of ether each time. The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water. The combined aqueous phases are made alkaline with aqueous ammonia solution and extracted three times with 100 ml of methylene chloride each time. The combined methylene chloride phases are dried over sodium sulfate and evaporated. There is obtained alpha-[4-(benzyloxy)-3-methoxyphenyl]-3-pyridinemethanol as an oil. The reaction mixture is stirred at -70° for 1 hour and at 0° for 2 hours The mixture is extracted three times with 50 ml of ether each time The combined ether phases are washed with 100 ml of 1N hydrochloric acid and 20 ml of water extracted three times with 100 ml of methylene chloride each time The combined methylene chloride phases are dried over sodium sulfate evaporated

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

Procedure: A solution of 2 (4.0 g, 13.7 mmol) in dry THF (40 mL) at −78° C. was treated with n-BuLi (2.5 M, 6.0 mL, 15.0 mmol) for 15 min to produce 3. To this solution, 5 (3.1 g, 12.2 mmol) in dry THF (40 mL) was added slowly over a 10 min period. The reaction mixture turned light brown in color and stirring was continued for 1 h. The reaction was quenched by the addition of saturated aqueous NH4Cl (10 mL) and the organic layer was separated. The aqueous layer was extracted with EtOAc (3×25 mL) and the combined organic layer was washed with brine (15 mL). Volatiles were evaporated under reduced pressure and the crude residue was purified by column chromatography using 20% acetone/hexane as the eluent to afford the title compound 6 as a white solid (2.6 g, 46%). to produce 3 The reaction was quenched by the addition of saturated aqueous NH4Cl (10 mL) the organic layer was separated The aqueous layer was extracted with EtOAc (3×25 mL) the combined organic layer was washed with brine (15 mL) Volatiles were evaporated under reduced pressure the crude residue was purified by column chromatography

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

Procedure: A solution of 2 (4.0 g, 13.7 mmol) in dry THF (40 mL) at −78° C. was treated with n-BuLi (2.5 M, 6.0 mL, 15.0 mmol) for 15 min to produce 3. To this solution, 5 (3.1 g, 12.2 mmol) in dry THF (40 mL) was added slowly over a 10 min period. The reaction mixture turned light brown in color and stirring was continued for 1 h. The reaction was quenched by the addition of saturated aqueous NH4Cl (10 mL) and the organic layer was separated. The aqueous layer was extracted with EtOAc (3×25 mL) and the combined organic layer was washed with brine (15 mL). Volatiles were evaporated under reduced pressure and the crude residue was purified by column chromatography using 20% acetone/hexane as the eluent to afford the title compound 6 as a white solid (2.6 g, 46%). to produce 3 The reaction was quenched by the addition of saturated aqueous NH4Cl (10 mL) the organic layer was separated The aqueous layer was extracted with EtOAc (3×25 mL) the combined organic layer was washed with brine (15 mL) Volatiles were evaporated under reduced pressure the crude residue was purified by column chromatography