3-bromo-N-methylaniline

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

Procedure: 166 mL (0.242 mol, 1.2 eq) of 1.6 M methyllithium in diethyl ether are added to a solution cooled to −70° C. of 37.6 g (0.202 mol, 1 eq) of 3-bromo-N-methylaniline (prepared in Example 7c) in 300 ml of tetrahydrofuran. The reaction medium is stirred at −70° C. for one hour and 306 mL (0.444 mol, 2.2 eq) of 1.5 M tert-butyllithium in diethyl ether are then added. The reaction medium is stirred at −70° C. for 45 minutes and 103.5 mL (0.808 mol, 4 eq) of trimethyl borate are then added. The reaction medium is stirred at room temperature for one hour and then hydrolyzed by addition of ice, acidified with 1 L of 2N hydrochloric acid and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over magnesium sulfate. The solvent is evaporated off and 4.2 g (14%) of 3-(methylamino)phenylboronic acid are obtained. The aqueous phase is basified and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over magnesium sulfate. The solvent is evaporated off and the residue is chromatographed on silica gel (8/2 heptane/ethyl acetate). 3.4 g (11%) of 3-(methylamino)phenylboronic acid are obtained. The reaction medium is stirred at −70° C. for 45 minutes The reaction medium is stirred at room temperature for one hour hydrolyzed by addition of ice extracted with ethyl acetate washed with water dried over magnesium sulfate The solvent is evaporated off

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

Procedure: 166 mL (0.242 mol, 1.2 eq) of 1.6 M methyllithium in diethyl ether are added to a solution cooled to −70° C. of 37.6 g (0.202 mol, 1 eq) of 3-bromo-N-methylaniline (prepared in Example 7c) in 300 ml of tetrahydrofuran. The reaction medium is stirred at −70° C. for one hour and 306 mL (0.444 mol, 2.2 eq) of 1.5 M tert-butyllithium in diethyl ether are then added. The reaction medium is stirred at −70° C. for 45 minutes and 103.5 mL (0.808 mol, 4 eq) of trimethyl borate are then added. The reaction medium is stirred at room temperature for one hour and then hydrolyzed by addition of ice, acidified with 1 L of 2N hydrochloric acid and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over magnesium sulfate. The solvent is evaporated off and 4.2 g (14%) of 3-(methylamino)phenylboronic acid are obtained. The aqueous phase is basified and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over magnesium sulfate. The solvent is evaporated off and the residue is chromatographed on silica gel (8/2 heptane/ethyl acetate). 3.4 g (11%) of 3-(methylamino)phenylboronic acid are obtained. The reaction medium is stirred at −70° C. for 45 minutes The reaction medium is stirred at room temperature for one hour hydrolyzed by addition of ice extracted with ethyl acetate washed with water dried over magnesium sulfate The solvent is evaporated off

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

Procedure: 3.6 g (12.7 mmol) of tert-butyl (3-bromophenyl)-N-methylcarbamate, prepared in a manner analogous to Example 1b), are dissolved in 15 ml of dichloromethane. 5 ml of trifluoroacetic acid are added and the reaction mixture is stirred at ambient temperature for 1 hour. The reaction is halted by the addition of 50 ml of a saturated sodium hydrogencarbonate solution and then extraction is carried out with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated and then the residue is chromatographed on silica gel (heptane/ethyl acetate 50/50). 2.14 g of 3-bromo-N-methylaniline are obtained in the form of an oil. Yield=90%. extraction dried over sodium sulfate The solvents are evaporated the residue is chromatographed on silica gel (heptane/ethyl acetate 50/50)

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

Procedure: In a manner similar to that of Example 1(e), by reacting 4.3 g (23.2 mmol) of (3-bromophenyl)-methylamine with 5.2 g (34.8 mmol) of 4-formylbenzene-boronic acid, 2.9 g (60%) of the expected product are obtained.

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

Procedure: In a manner similar to that of Example 1(e), by reacting 4.3 g (23.2 mmol) of (3-bromophenyl)-methylamine with 5.2 g (34.8 mmol) of 4-formylbenzene-boronic acid, 2.9 g (60%) of the expected product are obtained.

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

Procedure: 166 mL (0.242 mol, 1.2 eq) of 1.6 M methyllithium in diethyl ether are added to a solution cooled to −70° C. of 37.6 g (0.202 mol, 1 eq) of 3-bromo-N-methylaniline (prepared in Example 7c) in 300 ml of tetrahydrofuran. The reaction medium is stirred at −70° C. for one hour and 306 mL (0.444 mol, 2.2 eq) of 1.5 M tert-butyllithium in diethyl ether are then added. The reaction medium is stirred at −70° C. for 45 minutes and 103.5 mL (0.808 mol, 4 eq) of trimethyl borate are then added. The reaction medium is stirred at room temperature for one hour and then hydrolyzed by addition of ice, acidified with 1 L of 2N hydrochloric acid and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over magnesium sulfate. The solvent is evaporated off and 4.2 g (14%) of 3-(methylamino)phenylboronic acid are obtained. The aqueous phase is basified and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over magnesium sulfate. The solvent is evaporated off and the residue is chromatographed on silica gel (8/2 heptane/ethyl acetate). 3.4 g (11%) of 3-(methylamino)phenylboronic acid are obtained. The reaction medium is stirred at −70° C. for 45 minutes The reaction medium is stirred at room temperature for one hour hydrolyzed by addition of ice extracted with ethyl acetate washed with water dried over magnesium sulfate The solvent is evaporated off

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

Procedure: A solution of 3-bromo-N-methyl aniline (made as described by Lopez et al. in Tet. Lett., 1999, 40, 11, p2071-2074 incorporated herein by reference; 7.4 g, 39.5 mmol) in formic acid (20 mL) was refluxed for 3 h. The reaction mixture was then cooled to ambient temperature, diluted with water and extracted with diethyl ether. The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a dark brown oil. extracted with diethyl ether The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine dried over anhydrous magnesium sulfate filtered evaporated in vacuo

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

Procedure: A solution of 3-bromo-N-methyl aniline (made as described by Lopez et al. in Tet. Lett., 1999, 40, 11, p2071-2074 incorporated herein by reference; 7.4 g, 39.5 mmol) in formic acid (20 mL) was refluxed for 3 h. The reaction mixture was then cooled to ambient temperature, diluted with water and extracted with diethyl ether. The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a dark brown oil. extracted with diethyl ether The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine dried over anhydrous magnesium sulfate filtered evaporated in vacuo

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

Procedure: A solution of 3-bromo-N-methyl aniline (made as described by Lopez et al. in Tet. Lett., 1999, 40, 11, p 2071-2074 incorporated herein by reference; 7.4 g, 39.5 mmol) in formic acid (20 mL) was refluxed for 3 h. The reaction mixture was then cooled to ambient temperature, diluted with water and extracted with diethyl ether. The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a dark brown oil. extracted with diethyl ether The organic phase was washed with saturated, aqueous sodium bicarbonate solution, water and brine dried over anhydrous magnesium sulfate filtered evaporated in vacuo

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

Procedure: 2 g (11.6 mmol) 3-Bromoaniline is dissolved in 15 mL DMF and treated with 716 mg (1.1 eq.) KOH and 0.722 mL (1 eq.) iodomethane under continuous stirring at room temperature for 20 hours. The reaction mixture is extracted with ethyl acetate and water, the combined organic phases are washed with brine and dried with sodium sulfate and evaporated to dryness. The residue is column chromatographed (ethyl acetate/petroleum ether 2:5) to yield after evaporation the desired product as a yellow oil. The reaction mixture is extracted with ethyl acetate and water the combined organic phases are washed with brine dried with sodium sulfate evaporated to dryness chromatographed (ethyl acetate/petroleum ether 2:5) to yield after evaporation the desired product as a yellow oil

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

Procedure: Starting from 5-chloro-benzo[1,2,5]oxadiazole and (3-bromo-phenyl)-methyl-amine. Yellow powder. MS(ES+): 226 (M+1).

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

Procedure: Starting from 5-benzo[1,2,5]oxadiazoleboronic acid and (3-bromo-phenyl)-methyl-amine. Yellow powder. MS(ES+): 226 (M+1).