1-(2-bromophenyl)-N,N-dimethylmethanamine

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

Procedure: Dimethylamine (33% w/w in methanol) (25 ml) was added to 2-bromobenzylbromide (7.5 g 30 mmol) at 0° C. in methanol (35 ml), and the solution stirred for 30 min., evaporated, diluted with water and extracted twice with diethyl ether. The combined extracts were dried over sodium sulphate and evaporated to give product as a yellow oil (6.0 g). M+ 215/213; 360 MHz 1H n.m.r (CDCl3) 7.54 (1H, dd, J 1.2, 8.0 Hz), 7.42 (1H, dd, J 1.6, 7.6 Hz), 7.30-7.26 (1H, m), 7.11 (1H, dt, J 1.7, 7.7 Hz), 3.52 (2H, s), 2.30 (6H, s). evaporated diluted with water extracted twice with diethyl ether The combined extracts were dried over sodium sulphate evaporated

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

Procedure: Dimethylamine (33% w/w in methanol) (25 ml) was added to 2-bromobenzylbromide (7.5 g 30 mmol) at 0° C. in methanol (35 ml), and the solution stirred for 30 min., evaporated, diluted with water and extracted twice with diethyl ether. The combined extracts were dried over sodium sulphate and evaporated to give product as a yellow oil (6.0 g). M+ 215/213; 360 MHz 1H n.m.r (CDCl3) 7.54 (1H, dd, J 1.2, 8.0 Hz), 7.42 (1H, dd, J 1.6, 7.6 Hz), 7.30-7.26 (1H, m), 7.11 (1H, dt, J 1.7, 7.7 Hz), 3.52 (2H, s), 2.30 (6H, s). evaporated diluted with water extracted twice with diethyl ether The combined extracts were dried over sodium sulphate evaporated

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.2 g (94.2 mmol) of the (2-bromobenzyl)dimethylamine prepared according to example 1 (2nd stage) were dissolved in 350 ml tetrahydrofuran and the solution was cooled to −70° C. in a cooling bath (isopropanol/dry ice). 68 ml (108 mmol) butyllithium solution (1.6 M in hexane) were added dropwise under nitrogen such that the temperature did not rise above −60° C. After the mixture had been stirred at −70° C. for two hours, 32 ml (282 mmol) trimethyl borate were also added dropwise such that the temperature did not rise above −60° C. The mixture was warmed to 25° C. in the course of 15 hours and the solution was concentrated on a rotary evaporator (500-10 mbar) without heat being supplied. The residue was taken up in 200 ml n-hexane, the mixture was stirred for one hour and filtered over an inert gas frit under nitrogen and the filtrate was concentrated on a rotary evaporator (500-10 mbar) without heat being supplied. 12.0 g dimethyl 2-(dimethylaminomethyl)benzeneboronate (61.5% of theory) were obtained in this manner. did not rise above −60° C did not rise above −60° C The mixture was warmed to 25° C. in the course of 15 hours the solution was concentrated on a rotary evaporator (500-10 mbar) without heat the mixture was stirred for one hour filtered over an inert gas frit under nitrogen the filtrate was concentrated on a rotary evaporator (500-10 mbar) without heat

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.2 g (94.2 mmol) of the (2-bromobenzyl)dimethylamine prepared according to example 1 (2nd stage) were dissolved in 350 ml tetrahydrofuran and the solution was cooled to −70° C. in a cooling bath (isopropanol/dry ice). 68 ml (108 mmol) butyllithium solution (1.6 M in hexane) were added dropwise under nitrogen such that the temperature did not rise above −60° C. After the mixture had been stirred at −70° C. for two hours, 32 ml (282 mmol) trimethyl borate were also added dropwise such that the temperature did not rise above −60° C. The mixture was warmed to 25° C. in the course of 15 hours and the solution was concentrated on a rotary evaporator (500-10 mbar) without heat being supplied. The residue was taken up in 200 ml n-hexane, the mixture was stirred for one hour and filtered over an inert gas frit under nitrogen and the filtrate was concentrated on a rotary evaporator (500-10 mbar) without heat being supplied. 12.0 g dimethyl 2-(dimethylaminomethyl)benzeneboronate (61.5% of theory) were obtained in this manner. did not rise above −60° C did not rise above −60° C The mixture was warmed to 25° C. in the course of 15 hours the solution was concentrated on a rotary evaporator (500-10 mbar) without heat the mixture was stirred for one hour filtered over an inert gas frit under nitrogen the filtrate was concentrated on a rotary evaporator (500-10 mbar) without heat

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

Procedure: To a solution of 2-dimethylaminomethyl-bromobenzene (588 mg, 2.75 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (560 mg, 2.56 mmol) in toluene (10 mL) and n-BuOH (3 mL), Cs2CO3 (2.50 g, 7.67 mmol) in H2O (5 mL) was added, followed by addition of Pd(Ph3P)4 (200 mg, 0.17 mmol, 6%). The mixture was then heated at reflux for 4 h. EtOAc and H2O were added. The organic layer was separated, filtered, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel flash column using 50% EtOAc/hexanes (containing 1% TEA) as eluent to give a solid (300 mg). MS 182.0 (M—Me2N). The mixture was then heated at reflux for 4 h The organic layer was separated filtered dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel flash column

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

Procedure: To a solution of 2-dimethylaminomethyl-bromobenzene (588 mg, 2.75 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (560 mg, 2.56 mmol) in toluene (10 mL) and n-BuOH (3 mL), Cs2CO3 (2.50 g, 7.67 mmol) in H2O (5 mL) was added, followed by addition of Pd(Ph3P)4 (200 mg, 0.17 mmol, 6%). The mixture was then heated at reflux for 4 h. EtOAc and H2O were added. The organic layer was separated, filtered, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel flash column using 50% EtOAc/hexanes (containing 1% TEA) as eluent to give a solid (300 mg). MS 182.0 (M—Me2N). The mixture was then heated at reflux for 4 h The organic layer was separated filtered dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel flash column

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

Procedure: Dimethylamine (33% w/w in methanol) (25 ml) was added to 2-bromobenzylbromide (7.5 g 30 mmol) at 0° C. in methanol (35 ml), and the solution stirred for 30 min., evaporated, diluted with water and extracted twice with diethyl ether. The combined extracts were dried over sodium sulphate and evaporated to give product as a yellow oil (6.0 g). M+ 215/213; 360 MHz 1H n.m.r (CDCl3) 7.54 (1H, dd, J 1.2, 8.0 Hz), 7.42 (1H, dd, J 1.6, 7.6 Hz), 7.30-7.26 (1H, m), 7.11 (1H, dt, J 1.7, 7.7 Hz), 3.52 (2H, s), 2.30 (6H, s). evaporated diluted with water extracted twice with diethyl ether The combined extracts were dried over sodium sulphate evaporated

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.2 g (94.2 mmol) of the (2-bromobenzyl)dimethylamine prepared according to example 1 (2nd stage) were dissolved in 350 ml tetrahydrofuran and the solution was cooled to −70° C. in a cooling bath (isopropanol/dry ice). 68 ml (108 mmol) butyllithium solution (1.6 M in hexane) were added dropwise under nitrogen such that the temperature did not rise above −60° C. After the mixture had been stirred at −70° C. for two hours, 32 ml (282 mmol) trimethyl borate were also added dropwise such that the temperature did not rise above −60° C. The mixture was warmed to 25° C. in the course of 15 hours and the solution was concentrated on a rotary evaporator (500-10 mbar) without heat being supplied. The residue was taken up in 200 ml n-hexane, the mixture was stirred for one hour and filtered over an inert gas frit under nitrogen and the filtrate was concentrated on a rotary evaporator (500-10 mbar) without heat being supplied. 12.0 g dimethyl 2-(dimethylaminomethyl)benzeneboronate (61.5% of theory) were obtained in this manner. did not rise above −60° C did not rise above −60° C The mixture was warmed to 25° C. in the course of 15 hours the solution was concentrated on a rotary evaporator (500-10 mbar) without heat the mixture was stirred for one hour filtered over an inert gas frit under nitrogen the filtrate was concentrated on a rotary evaporator (500-10 mbar) without heat