7-chloroheptylbenzene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.07 g of 7-chloroheptylbenzene and 0.89 g of 4-chlorobenzoyl chloride were dissolved in 10 ml of nitrobenzene and treated with 0.82 g of aluminium chloride under argon and while cooling with ice. The mixture was then stirred at room temperature for 18 hours, taken up in 100 ml of ice-cold 2N hydrochloric acid solution and extracted three times with 50 ml of ether each time. The organic phases were washed with 50 ml of a 10 percent sodium bicarbonate solution and 50 ml of a saturated sodium chloride solution, dried over magnesium sulphate and concentrated. The nitrobenzene was removed by distillation at 80°-100° C. and 20 Pa. By distillation at 240°-250° C. and about 13.4 Pa there were obtained 1.32 g (74%) of 4-chloro-4'-(7-chloroheptyl)benzophenone as a light yellow oil. while cooling with ice extracted three times with 50 ml of ether each time The organic phases were washed with 50 ml of a 10 percent sodium bicarbonate solution and 50 ml of a saturated sodium chloride solution dried over magnesium sulphate concentrated The nitrobenzene was removed by distillation at 80°-100° C. By distillation at 240°-250° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 8.25 g. of ethyl p-aminobenzoate, 5.06 g. of 7-phenylheptylchloride, 3.6 g. of sodium iodide and 25 ml. of hexamethylphosphoramide is heated in an oil bath at 110° C. for 20 hours. The mixture is chilled, diluted with 30 ml. of ethanol-water (1:1) and with water to give crystals, m.p. 65°-67° C. Recrystallization from ethanol gives white crystals, m.p. 66.5°-68° C. A mixture of 8.25 g The mixture is chilled diluted with 30 ml Recrystallization from ethanol gives white crystals, m.p. 66.5°-68° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 8.25 g. of ethyl p-aminobenzoate, 5.06 g. of 7-phenylheptylchloride, 3.6 g. of sodium iodide and 25 ml. of hexamethylphosphoramide is heated in an oil bath at 110° C. for 20 hours. The mixture is chilled, diluted with 30 ml. of ethanol-water (1:1) and with water to give crystals, m.p. 65°-67° C. Recrystallization from ethanol gives white crystals, m.p. 66.5°-68° C. A mixture of 8.25 g The mixture is chilled diluted with 30 ml Recrystallization from ethanol gives white crystals, m.p. 66.5°-68° C.

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (21.0 g, 0.12 mol) in tetrahydrofuran (75 mL), n-BuLi (1.54M, 78 mL, 0.12 mol) was added over 1 h such that the temperature was maintained between 20°-30° C. with cooling. The mixture was stirred for 30 min and 1-chloro-7-phenylheptane (21.05 g, 0.1 mol) in tetrahydrofuran (40 mL) was added quickly. The mixture was heated at 50° C. for 3 h and quenched by the slow addition of dilute hydrochloric acid. Hydrolysis was completed by heating the mixture at 50°-60° C. for 2.5 h. The mixture was cooled to ambient temperature and the organic phase separated. The aqueous phase was extracted with hexane, and the combined organic extracts were washed with water. The extracts were dried over magnesium sulphate and, after filtering and washing the filter cake with hexane, the organic solution was concentrated under vacuum to give 2-(8-phenyloctyl)benzaldehyde as an oil (34.56 g, 65.3% pure by HPLC assay, 77% corrected yield). was maintained between 20°-30° C. with cooling quenched by the slow addition of dilute hydrochloric acid Hydrolysis by heating the mixture at 50°-60° C. for 2.5 h The mixture was cooled to ambient temperature the organic phase separated The aqueous phase was extracted with hexane the combined organic extracts were washed with water The extracts were dried over magnesium sulphate after filtering washing the filter cake with hexane the organic solution was concentrated under vacuum to give

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (21.0 g, 0.12 mol) in tetrahydrofuran (75 mL), n-BuLi (1.54M, 78 mL, 0.12 mol) was added over 1 h such that the temperature was maintained between 20°-30° C. with cooling. The mixture was stirred for 30 min and 1-chloro-7-phenylheptane (21.05 g, 0.1 mol) in tetrahydrofuran (40 mL) was added quickly. The mixture was heated at 50° C. for 3 h and quenched by the slow addition of dilute hydrochloric acid. Hydrolysis was completed by heating the mixture at 50°-60° C. for 2.5 h. The mixture was cooled to ambient temperature and the organic phase separated. The aqueous phase was extracted with hexane, and the combined organic extracts were washed with water. The extracts were dried over magnesium sulphate and, after filtering and washing the filter cake with hexane, the organic solution was concentrated under vacuum to give 2-(8-phenyloctyl)benzaldehyde as an oil (34.56 g, 65.3% pure by HPLC assay, 77% corrected yield). was maintained between 20°-30° C. with cooling quenched by the slow addition of dilute hydrochloric acid Hydrolysis by heating the mixture at 50°-60° C. for 2.5 h The mixture was cooled to ambient temperature the organic phase separated The aqueous phase was extracted with hexane the combined organic extracts were washed with water The extracts were dried over magnesium sulphate after filtering washing the filter cake with hexane the organic solution was concentrated under vacuum to give

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (11.2 g, 0.064 mol) and 2,2,6,6-tetra-methylpiperidine (0.9 g, 0.0064 mol) in tetrahydrofuran (40 mL) was cooled to -5° C. To this was added n-BuLi (1.6M, 40 mL, 0.064 mol) over 60 min from a syringe pump such that the temperature was maintained below 0° C. The mixture was stirred for 30 min and 1-chloro-7-phenylheptane (11.23 g, 0.053 mol) in tetrahydrofuran (20 mL) quickly added. The reaction mixture was heated at 50°-55° C. for 2 h. The reaction mixture was cooled to 40° C. and quenched by the slow addition of dilute hydrochloric acid (100 mL of acid diluted with 300 mL of water). Hydrolysis was completed by heating the mixture at 50°-60° C. for 2.5 h. The mixture was cooled to ambient temperature and the organic phase separated. The aqueous phase was extracted with hexane (100 mL) and the combined organic extracts washed with water (100 mL). The extracts were dried over magnesium sulphate and after filtering and washing the filter cake with hexane the organic solution was concentrated under vacuum to give 2-(8-phenyloctyl)benzaldehyde as an oil (14.5 g, 69.3% pure by HPLC assay, 87% corrected yield). was maintained below 0° C The reaction mixture was heated at 50°-55° C. for 2 h quenched by the slow addition of dilute hydrochloric acid (100 mL of acid diluted with 300 mL of water) Hydrolysis by heating the mixture at 50°-60° C. for 2.5 h The mixture was cooled to ambient temperature the organic phase separated The aqueous phase was extracted with hexane (100 mL) the combined organic extracts washed with water (100 mL) The extracts were dried over magnesium sulphate after filtering washing the filter cake with hexane the organic solution was concentrated under vacuum to give

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (11.2 g, 0.064 mol) and 2,2,6,6-tetra-methylpiperidine (0.9 g, 0.0064 mol) in tetrahydrofuran (40 mL) was cooled to -5° C. To this was added n-BuLi (1.6M, 40 mL, 0.064 mol) over 60 min from a syringe pump such that the temperature was maintained below 0° C. The mixture was stirred for 30 min and 1-chloro-7-phenylheptane (11.23 g, 0.053 mol) in tetrahydrofuran (20 mL) quickly added. The reaction mixture was heated at 50°-55° C. for 2 h. The reaction mixture was cooled to 40° C. and quenched by the slow addition of dilute hydrochloric acid (100 mL of acid diluted with 300 mL of water). Hydrolysis was completed by heating the mixture at 50°-60° C. for 2.5 h. The mixture was cooled to ambient temperature and the organic phase separated. The aqueous phase was extracted with hexane (100 mL) and the combined organic extracts washed with water (100 mL). The extracts were dried over magnesium sulphate and after filtering and washing the filter cake with hexane the organic solution was concentrated under vacuum to give 2-(8-phenyloctyl)benzaldehyde as an oil (14.5 g, 69.3% pure by HPLC assay, 87% corrected yield). was maintained below 0° C The reaction mixture was heated at 50°-55° C. for 2 h quenched by the slow addition of dilute hydrochloric acid (100 mL of acid diluted with 300 mL of water) Hydrolysis by heating the mixture at 50°-60° C. for 2.5 h The mixture was cooled to ambient temperature the organic phase separated The aqueous phase was extracted with hexane (100 mL) the combined organic extracts washed with water (100 mL) The extracts were dried over magnesium sulphate after filtering washing the filter cake with hexane the organic solution was concentrated under vacuum to give

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium tetrachlorocuprate [THF 33 L, lithium chloride (0.87 kg, 19.3 mol), cupric chloride (1.4 kg, 10.4 mol)] was added to a solution of benzylmagnesium chloride (160 L of 1.86M, 298 mol) in tetrahydrofuran at 15° C., and the mixture stirred for 30 min. Bromochlorohexane in toluene (85.5 kg of solution, 55% w/w by assay, 47.1 kg, 236 mol) was added over 3 h while maintaining the temperature between 15°-20° C. Stirring was continued for a further 1.25 h. 10% Ammonium chloride solution (263 L) was added over 1 h, maintaining the temperature below 30° C. The phases were separated and the organic phase further washed with ammonium chloride solution (170 L) and 20% sodium chloride solution (3×197 L). The organic solution was concentrated under vacuum to leave an oil (56.8 kg, 77% pure by HPLC assay, 88% corrected yield), which was distilled (b.p. 129°-132° C., 2 mbar) to yield the title compound (70%, 99% pure by GC assay). while maintaining the temperature between 15°-20° C Stirring was continued for a further 1.25 h maintaining the temperature below 30° C The phases were separated the organic phase further washed with ammonium chloride solution (170 L) and 20% sodium chloride solution (3×197 L) The organic solution was concentrated under vacuum to leave an oil (56.8 kg, 77% pure by HPLC assay, 88% corrected yield), which was distilled (b.p. 129°-132° C., 2 mbar)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium tetrachlorocuprate [THF 33 L, lithium chloride (0.87 kg, 19.3 mol), cupric chloride (1.4 kg, 10.4 mol)] was added to a solution of benzylmagnesium chloride (160 L of 1.86M, 298 mol) in tetrahydrofuran at 15° C., and the mixture stirred for 30 min. Bromochlorohexane in toluene (85.5 kg of solution, 55% w/w by assay, 47.1 kg, 236 mol) was added over 3 h while maintaining the temperature between 15°-20° C. Stirring was continued for a further 1.25 h. 10% Ammonium chloride solution (263 L) was added over 1 h, maintaining the temperature below 30° C. The phases were separated and the organic phase further washed with ammonium chloride solution (170 L) and 20% sodium chloride solution (3×197 L). The organic solution was concentrated under vacuum to leave an oil (56.8 kg, 77% pure by HPLC assay, 88% corrected yield), which was distilled (b.p. 129°-132° C., 2 mbar) to yield the title compound (70%, 99% pure by GC assay). while maintaining the temperature between 15°-20° C Stirring was continued for a further 1.25 h maintaining the temperature below 30° C The phases were separated the organic phase further washed with ammonium chloride solution (170 L) and 20% sodium chloride solution (3×197 L) The organic solution was concentrated under vacuum to leave an oil (56.8 kg, 77% pure by HPLC assay, 88% corrected yield), which was distilled (b.p. 129°-132° C., 2 mbar)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.07 g of 7-chloroheptylbenzene and 0.89 g of 4-chlorobenzoyl chloride were dissolved in 10 ml of nitrobenzene and treated with 0.82 g of aluminium chloride under argon and while cooling with ice. The mixture was then stirred at room temperature for 18 hours, taken up in 100 ml of ice-cold 2N hydrochloric acid solution and extracted three times with 50 ml of ether each time. The organic phases were washed with 50 ml of a 10 percent sodium bicarbonate solution and 50 ml of a saturated sodium chloride solution, dried over magnesium sulphate and concentrated. The nitrobenzene was removed by distillation at 80°-100° C. and 20 Pa. By distillation at 240°-250° C. and about 13.4 Pa there were obtained 1.32 g (74%) of 4-chloro-4'-(7-chloroheptyl)benzophenone as a light yellow oil. while cooling with ice extracted three times with 50 ml of ether each time The organic phases were washed with 50 ml of a 10 percent sodium bicarbonate solution and 50 ml of a saturated sodium chloride solution dried over magnesium sulphate concentrated The nitrobenzene was removed by distillation at 80°-100° C. By distillation at 240°-250° C.