N-tert-butyl-1-(2-methylphenyl)methanimine

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

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

Procedure: 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

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

Procedure: 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

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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

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

Procedure: ) To a solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (5.0 g, 0.03 mol) and N,N,N',N'-tetramethylethylene diamine (3.31 g, 0.03 mol) in tetrahydrofuran (40 mL), n-butyl lithium (2.5M, 11.4 mL, 0.03 mol) at 0° C. was slowly added. The solution was stirred for an additional 30 min followed by the quick addition of 1-bromo-7-phenylheptane (7.28 g, 0.03 mol) in tetrahydrofuran (10 mL). The reaction mixture was allowed to warm to room temperature and stirring was continued for 15 h. The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) and stirred for 30 min. The layers were separated, methylene chloride (50 mL) was added to the organic layer and the organics were washed with saturated brine solution (50 mL). The organics were then dried (magnesium sulfate), and concentrated to an oil to yield 2-(8-phenyloctyl)benzaldehyde (3.8 g, 45%): IR (neat film) 2920, 2880, 1695, 1600, 1455 cm-1 ; 1H NMR (CDCl3, 400 MHz) δ 10.25 (s, 1 H), 7.80 (dd, 1 H, J=1.2 and 7.7 Hz), 7.45 (m, 1 H), 7.33-7.13 (m, 7 H), 2.98 (t, 2 H, J=7.7 Hz), 2.58 (t, 2 H, J=7.7 Hz), 1.58 (m, 4 H), 1.30 (m, 8 H). stirring was continued for 15 h The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) stirred for 30 min The layers were separated methylene chloride (50 mL) was added to the organic layer the organics were washed with saturated brine solution (50 mL) The organics were then dried (magnesium sulfate) concentrated to an oil

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

Procedure: ) To a solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (5.0 g, 0.03 mol) and N,N,N',N'-tetramethylethylene diamine (3.31 g, 0.03 mol) in tetrahydrofuran (40 mL), n-butyl lithium (2.5M, 11.4 mL, 0.03 mol) at 0° C. was slowly added. The solution was stirred for an additional 30 min followed by the quick addition of 1-bromo-7-phenylheptane (7.28 g, 0.03 mol) in tetrahydrofuran (10 mL). The reaction mixture was allowed to warm to room temperature and stirring was continued for 15 h. The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) and stirred for 30 min. The layers were separated, methylene chloride (50 mL) was added to the organic layer and the organics were washed with saturated brine solution (50 mL). The organics were then dried (magnesium sulfate), and concentrated to an oil to yield 2-(8-phenyloctyl)benzaldehyde (3.8 g, 45%): IR (neat film) 2920, 2880, 1695, 1600, 1455 cm-1 ; 1H NMR (CDCl3, 400 MHz) δ 10.25 (s, 1 H), 7.80 (dd, 1 H, J=1.2 and 7.7 Hz), 7.45 (m, 1 H), 7.33-7.13 (m, 7 H), 2.98 (t, 2 H, J=7.7 Hz), 2.58 (t, 2 H, J=7.7 Hz), 1.58 (m, 4 H), 1.30 (m, 8 H). stirring was continued for 15 h The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) stirred for 30 min The layers were separated methylene chloride (50 mL) was added to the organic layer the organics were washed with saturated brine solution (50 mL) The organics were then dried (magnesium sulfate) concentrated to an oil

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

Procedure: To a stirred solution of diisopropylamine (29.14 g,0.289 mol) in tetrahydrofuran (450 mL) cooled to -5° C. was added n-butyllithium (2.5M, 114.3 mL, 0.286 mol) at a rate which maintained the solution temperature below 10° C. After the addition was complete, the solution was stirred 15 min with cooling. To this solution was added N-[(2-methylphenyl)-methylene]-1,1-dimethylethanamine (50.0 g, 0.286 mol) in tetrahydrofuran (65.0 mL) at such a rate as to keep the reaction temperature below 5° C. The reaction was stirred for 15 min with cooling then 1-bromo-7-phenylheptane (72.9 g, 0.286 mol) in tetrahydrofuran (75 mL) was quickly added. The reaction mixture was stirred for 1 h with cooling then allowed to warm to room temperature and stirred for an additional 14 h. The reaction mixture was assayed by gas chromatography for product imine (RT 19.8 min., DB-1, 30 m×0.53 mm, program, 100° C. for 5 min, 100°-260° C. at 15° C./min, hold at 260° C. for 12 min.). The product was isolated by dilution of the reaction mixture with water and methylene chloride, quickly washing the organic mixture with water, and concentrating the solution to an oil. The oil was purified by distillation. maintained the solution temperature below 10° C After the addition with cooling the reaction temperature below 5° C The reaction was stirred for 15 min with cooling The reaction mixture was stirred for 1 h with cooling stirred for an additional 14 h quickly washing the organic mixture with water concentrating the solution to an oil The oil was purified by distillation

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

Procedure: To a stirred solution of diisopropylamine (29.14 g,0.289 mol) in tetrahydrofuran (450 mL) cooled to -5° C. was added n-butyllithium (2.5M, 114.3 mL, 0.286 mol) at a rate which maintained the solution temperature below 10° C. After the addition was complete, the solution was stirred 15 min with cooling. To this solution was added N-[(2-methylphenyl)-methylene]-1,1-dimethylethanamine (50.0 g, 0.286 mol) in tetrahydrofuran (65.0 mL) at such a rate as to keep the reaction temperature below 5° C. The reaction was stirred for 15 min with cooling then 1-bromo-7-phenylheptane (72.9 g, 0.286 mol) in tetrahydrofuran (75 mL) was quickly added. The reaction mixture was stirred for 1 h with cooling then allowed to warm to room temperature and stirred for an additional 14 h. The reaction mixture was assayed by gas chromatography for product imine (RT 19.8 min., DB-1, 30 m×0.53 mm, program, 100° C. for 5 min, 100°-260° C. at 15° C./min, hold at 260° C. for 12 min.). The product was isolated by dilution of the reaction mixture with water and methylene chloride, quickly washing the organic mixture with water, and concentrating the solution to an oil. The oil was purified by distillation. maintained the solution temperature below 10° C After the addition with cooling the reaction temperature below 5° C The reaction was stirred for 15 min with cooling The reaction mixture was stirred for 1 h with cooling stirred for an additional 14 h quickly washing the organic mixture with water concentrating the solution to an oil The oil was purified by distillation

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

Procedure: To a stirred solution of diisopropylamine (29.14 g,0.289 mol) in tetrahydrofuran (450 mL) cooled to -5° C. was added n-butyllithium (2.5M, 114.3 mL, 0.286 mol) at a rate which maintained the solution temperature below 10° C. After the addition was complete, the solution was stirred 15 min with cooling. To this solution was added N-[(2-methylphenyl)-methylene]-1,1-dimethylethanamine (50.0 g, 0.286 mol) in tetrahydrofuran (65.0 mL) at such a rate as to keep the reaction temperature below 5° C. The reaction was stirred for 15 min with cooling then 1-bromo-7-phenylheptane (72.9 g, 0.286 mol) in tetrahydrofuran (75 mL) was quickly added. The reaction mixture was stirred for 1 h with cooling then allowed to warm to room temperature and stirred for an additional 14 h. The reaction mixture was assayed by gas chromatography for product imine (RT 19.8 min., DB-1, 30 m×0.53 mm, program, 100° C. for 5 min, 100°-260° C. at 15° C./min, hold at 260° C. for 12 min.). The product was isolated by dilution of the reaction mixture with water and methylene chloride, quickly washing the organic mixture with water, and concentrating the solution to an oil. The oil was purified by distillation. maintained the solution temperature below 10° C After the addition with cooling the reaction temperature below 5° C The reaction was stirred for 15 min with cooling The reaction mixture was stirred for 1 h with cooling stirred for an additional 14 h quickly washing the organic mixture with water concentrating the solution to an oil The oil was purified by distillation

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

Procedure: A stirred solution of o-tolualdehyde (25 g, 0.21 mol), and t-butylamine (27.75 g, 0.38 mol) in toluene (250 mL) was refluxed under standard Dean-Stark conditions for 20 h. The solution was evaporated to an oil which was vacuum distilled (bp 70°-73° C., 0.6 mm Hg) to afford 33.9 g (93%) of product: IR (neat) 2980, 1645, 1605, 1460, 1375, 1210, 960, 910 cm-1 ; 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1 H), 7.86-7.83 (m, 1 H), 7.25-7.11 (m, 3 H), 2.46 (s, 3 H), 1.30 (s, 9 H); 13C NMR (CDCl3, 100 MHz) δ 153.7, 137.1, 135.1, 130.5, 129.6, 127.1, 126.4, 57.5, 29.8, 19.2; GC RT 7.6 min (DB-1, 30 m×0.53 mm, program: 100° C. for 5 min, 100°-260° C. at 15° C./min, hold at 260° C. for 12 min). The solution was evaporated to an oil which distilled (bp 70°-73° C., 0.6 mm Hg)