1-bromo-4-butylbenzene

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:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of Intermediate A (3.52 g, 10 mmol), 9,9-dihexylfluorene-2,7-diboronic acid (1.90 g, 4.5 mmol), sodium carbonate (2.12 g, 20 mmol) in water (10 mL), tetrakis(triphenylphosphine)palladium (0) (1.00 g, 0.86 mmol), n-butanol (80 mL), and toluene (20 mL) was stirred and heated under argon at 110° C. After 48 hours, 1-bromo-4-butylbenzene (3.0 mL, 17 mmol) was added followed by sodium carbonate (2.12 g, 20 mmol) in water (10 mL) and tetrakis(triphenylphosphine)palladium (0) (1.00 g, 0.86 mmol), and heating was continued for an additional 20 hours. The reaction mixture was poured into water (200 mL and extracted with ethyl acetate). The extract was dried over anhydrous sodium sulfate, the volatiles were removed under reduced pressure, and the residue was chromatographed (silica gel, dichloromethane/ethyl acetate 3:1). The first fraction gave Intermediate E (414 mg, 10%). heating was continued for an additional 20 hours The extract was dried over anhydrous sodium sulfate the volatiles were removed under reduced pressure the residue was chromatographed (silica gel, dichloromethane/ethyl acetate 3:1)

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

Procedure: Palladium acetate, tri-o-tolylphosphine and toluene were charged in a three-necked round-bottomed flask, and stirred for 20 minutes at room temperature. Phenoxazine, 1-bromo-4-butylbenzene, sodium t-butoxide and toluene were added, and the mixture was heated in an oil bath and refluxed for 15 hours. After cooling, concentrated hydrochloric acid was added and the mixture was stirred for 1 hour, then, the solution was passed through a neutral alumina column. The column was washed with toluene, and the solvent was removed using a rotary evaporator, to obtain yellow solid. The solid was re-crystallized from toluene/methanol, to obtain N-(4-n-butylphenyl)phenoxazine. the mixture was heated in an oil bath refluxed for 15 hours After cooling the mixture was stirred for 1 hour The column was washed with toluene the solvent was removed a rotary evaporator to obtain yellow solid The solid was re-crystallized from toluene/methanol

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

Procedure: Palladium acetate, tri-o-tolylphosphine and toluene were charged in a three-necked round-bottomed flask, and stirred for 20 minutes at room temperature. Phenoxazine, 1-bromo-4-butylbenzene, sodium t-butoxide and toluene were added, and the mixture was heated in an oil bath and refluxed for 15 hours. After cooling, concentrated hydrochloric acid was added and the mixture was stirred for 1 hour, then, the solution was passed through a neutral alumina column. The column was washed with toluene, and the solvent was removed using a rotary evaporator, to obtain yellow solid. The solid was re-crystallized from toluene/methanol, to obtain N-(4-n-butylphenyl)phenoxazine. the mixture was heated in an oil bath refluxed for 15 hours After cooling the mixture was stirred for 1 hour The column was washed with toluene the solvent was removed a rotary evaporator to obtain yellow solid The solid was re-crystallized from toluene/methanol

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

Procedure: To a solution of 3-ethoxycarbonyl-2,6-dimethyl-1H-pyridin-4-one (9.7 g) in dichloromethane (200 mL) were added benzyl bromide (8.9 mL) and silver carbonate (41 g), and the mixture was stirred for 2 hours at 50° C. under shading. The reaction mixture was cooled to room temperature, and the insoluble material was removed by filtration. After the filtrate was concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1) to give 4-benzyloxy-3-ethoxy-carbonyl-2,6-dimethylpyridine (8.6 g). To a solution of the obtained 4-benzyloxy-3-ethoxycarbonyl-2,6-dimethylpyridine (8.6 g) in tetrahydrofuran (60 mL) was added diisobutylaluminum hydride (1.5 mol/L solution in toluene, 50 mL) at 0° C. The temperature was raised to room temperature, and the reaction mixture was stirred for additionally 40 minutes. After the reaction mixture was poured into 2 mol/L hydrochloric acid (68 mL), 2 mol/L aqueous sodium hydroxide solution (130 mL) was added to the mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 4-benzyloxy-3-hydroxymethyl-2,6-dimethyl-pyridine (7.2 g). To a solution of the obtained 4-benzyloxy-3-hydroxymethyl-2,6-dimethylpyridine (7.2 g) in dichloromethane (120 mL) was added a Dess-Martin reagent (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one)(15 g), and the mixture was stirred for 6.5 hours at room temperature. To the reaction mixture were added saturated aqueous sodium bicarbonate solution (150 mL) and 10% sodium thiosulfate (150 mL), and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/2) to give 4-benzyloxy-3-formyl-2,6-dimethylpyridine (5.3 g). To a solution of 4-butyl-bromobenzene (0.052 g) in tetrahydrofuran (1.2 mL) was added tert-butyllithium (1.5 mol/L solution in hexane, 0.20 mL) at −78° C. under an argon atmosphere, and the mixture was stirred for 30 minutes at the same temperature. To the reaction mixture was added 4-benzyloxy-3-formyl-2,6-dimethylpyridine (0.048 g) in tetrahydrofuran (1.3 mL), and the mixture was stirred for, 50 minutes at 0° C. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography on silica gel (developing, solvent: hexane/ethyl acetate=1/2) to give 4-benzyloxy-2,6-dimethylpyridin-3-yl 4-butylphenyl methanol (0.043 g). To a solution of the obtained 4-benzyloxy-2,6-dimethylpyridin-3-yl 4-butylphenyl methanol (0.043 g) in ethanol (2.3 mL) was added 10% palladium carbon powder (0.085 g), and the mixture was stirred for 12 hours at room temperature under a hydrogen atmosphere. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography on silica gel (developing solvent: dichloromethane/methanol=8/1) to give, 3-(4-butylbenzyl)-2,6-dimethyl-1H-pyridin-4-one (0.027 g). the mixture was stirred for, 50 minutes at 0° C the mixture was extracted with diethyl ether The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by preparative thin layer chromatography on silica gel (developing, solvent: hexane/ethyl acetate=1/2)

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

Procedure: To a solution of 3-ethoxycarbonyl-2,6-dimethyl-1H-pyridin-4-one (9.7 g) in dichloromethane (200 mL) were added benzyl bromide (8.9 mL) and silver carbonate (41 g), and the mixture was stirred for 2 hours at 50° C. under shading. The reaction mixture was cooled to room temperature, and the insoluble material was removed by filtration. After the filtrate was concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1) to give 4-benzyloxy-3-ethoxy-carbonyl-2,6-dimethylpyridine (8.6 g). To a solution of the obtained 4-benzyloxy-3-ethoxycarbonyl-2,6-dimethylpyridine (8.6 g) in tetrahydrofuran (60 mL) was added diisobutylaluminum hydride (1.5 mol/L solution in toluene, 50 mL) at 0° C. The temperature was raised to room temperature, and the reaction mixture was stirred for additionally 40 minutes. After the reaction mixture was poured into 2 mol/L hydrochloric acid (68 mL), 2 mol/L aqueous sodium hydroxide solution (130 mL) was added to the mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 4-benzyloxy-3-hydroxymethyl-2,6-dimethyl-pyridine (7.2 g). To a solution of the obtained 4-benzyloxy-3-hydroxymethyl-2,6-dimethylpyridine (7.2 g) in dichloromethane (120 mL) was added a Dess-Martin reagent (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one)(15 g), and the mixture was stirred for 6.5 hours at room temperature. To the reaction mixture were added saturated aqueous sodium bicarbonate solution (150 mL) and 10% sodium thiosulfate (150 mL), and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/2) to give 4-benzyloxy-3-formyl-2,6-dimethylpyridine (5.3 g). To a solution of 4-butyl-bromobenzene (0.052 g) in tetrahydrofuran (1.2 mL) was added tert-butyllithium (1.5 mol/L solution in hexane, 0.20 mL) at −78° C. under an argon atmosphere, and the mixture was stirred for 30 minutes at the same temperature. To the reaction mixture was added 4-benzyloxy-3-formyl-2,6-dimethylpyridine (0.048 g) in tetrahydrofuran (1.3 mL), and the mixture was stirred for, 50 minutes at 0° C. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography on silica gel (developing, solvent: hexane/ethyl acetate=1/2) to give 4-benzyloxy-2,6-dimethylpyridin-3-yl 4-butylphenyl methanol (0.043 g). To a solution of the obtained 4-benzyloxy-2,6-dimethylpyridin-3-yl 4-butylphenyl methanol (0.043 g) in ethanol (2.3 mL) was added 10% palladium carbon powder (0.085 g), and the mixture was stirred for 12 hours at room temperature under a hydrogen atmosphere. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography on silica gel (developing solvent: dichloromethane/methanol=8/1) to give, 3-(4-butylbenzyl)-2,6-dimethyl-1H-pyridin-4-one (0.027 g). the mixture was stirred for, 50 minutes at 0° C the mixture was extracted with diethyl ether The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by preparative thin layer chromatography on silica gel (developing, solvent: hexane/ethyl acetate=1/2)

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

Procedure: A 2 L 3 neck round bottom flask equipped with overhead stirrer, reflux condensor and a nitrogen line was charged with 0.948 g (4.216 mmol) palladium acetate and 2.647 g (8.746 mmol) tri-o-tolylphosphine and 50 ml toluene. The mixture was stirred at ambient temperature for 20 minutes until an orange-red solution was formed. At that time, phenothiazine (19.93 g, 100 mmol), 1-bromo-4-butyl benzene (23.6 g, 110 mmol) and sodium t-butoxide (10.71 g, 100 mmol) along with 1000 mL toluene was added. The reaction was placed in an oil bath and heated to reflux for 15 hours. A sample was taken for HPLC showing that all starting material was gone. A major peak with the retention time of 8.6 minutes was seen. The solution was cooled. 15 mL concentrated HCl was added. The solution was stirred for an additional hour. Then the solution was passed through a neutral alumina column (750 g). The column was rinsed with toluene. The solvent was removed using a rotary evaporator to yield a yellow solid. The solid was recrystallized from toulene/MeOH. 19.6 g of white solid was obtained with 99% purity. The yield was 60.6%. MS: 331. 1H NMR (DMSO) δ0.92 (t, 3H), 1.36 (m, 2H), 1.62 (m, 2H), 2.73 (t, 2H), 6.13 (d, 2H), 6.87(m, 4H), 7.05 (d, 2H), 7.30 (d, 2H), 7.47 (d, 2H). reflux condensor was formed The reaction was placed in an oil bath heated to reflux for 15 hours The solution was cooled The solution was stirred for an additional hour The column was rinsed with toluene The solvent was removed a rotary evaporator to yield a yellow solid The solid was recrystallized from toulene/MeOH

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

Procedure: A 2 L 3 neck round bottom flask equipped with overhead stirrer, reflux condensor and a nitrogen line was charged with 0.948 g (4.216 mmol) palladium acetate and 2.647 g (8.746 mmol) tri-o-tolylphosphine and 50 ml toluene. The mixture was stirred at ambient temperature for 20 minutes until an orange-red solution was formed. At that time, phenothiazine (19.93 g, 100 mmol), 1-bromo-4-butyl benzene (23.6 g, 110 mmol) and sodium t-butoxide (10.71 g, 100 mmol) along with 1000 mL toluene was added. The reaction was placed in an oil bath and heated to reflux for 15 hours. A sample was taken for HPLC showing that all starting material was gone. A major peak with the retention time of 8.6 minutes was seen. The solution was cooled. 15 mL concentrated HCl was added. The solution was stirred for an additional hour. Then the solution was passed through a neutral alumina column (750 g). The column was rinsed with toluene. The solvent was removed using a rotary evaporator to yield a yellow solid. The solid was recrystallized from toulene/MeOH. 19.6 g of white solid was obtained with 99% purity. The yield was 60.6%. MS: 331. 1H NMR (DMSO) δ0.92 (t, 3H), 1.36 (m, 2H), 1.62 (m, 2H), 2.73 (t, 2H), 6.13 (d, 2H), 6.87(m, 4H), 7.05 (d, 2H), 7.30 (d, 2H), 7.47 (d, 2H). reflux condensor was formed The reaction was placed in an oil bath heated to reflux for 15 hours The solution was cooled The solution was stirred for an additional hour The column was rinsed with toluene The solvent was removed a rotary evaporator to yield a yellow solid The solid was recrystallized from toulene/MeOH