2-(bromomethyl)-5-fluoro-1,3-dimethylbenzene

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:; See reaction.notes.procedure_details.

Procedure: A solution of 1.86 g (9 mmol) 2,6-dimethyl-4-fluoro-benzyl bromide and 0.420 g (9 mmol) sodium cyanide in 21 ml ethanol/water 6:1 was heated to reflux for 4h. The cooled reaction mixture was concentrated and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. Filtration of the residue through a silica gel pad with heptane/ethyl acetate 1:1 provided (4-fluoro-2,6-dimethyl-phenyl)-acetonitrile as colourless solid: MS (EI): 163.1 (M+.), 148.1 ((M-CH3)+.), 136.1 ((M-HCN)+., 100%). to reflux for 4h The cooled reaction mixture was concentrated extracted with ethyl acetate The combined extracts were washed with brine dried over Na2SO4 filtered evaporated Filtration of the residue through a silica gel pad with heptane/ethyl acetate 1:1 provided (4-fluoro-2,6-dimethyl-phenyl)-acetonitrile as colourless solid

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

Procedure: A solution of 1.86 g (9 mmol) 2,6-dimethyl-4-fluoro-benzyl bromide and 0.420 g (9 mmol) sodium cyanide in 21 ml ethanol/water 6:1 was heated to reflux for 4h. The cooled reaction mixture was concentrated and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. Filtration of the residue through a silica gel pad with heptane/ethyl acetate 1:1 provided (4-fluoro-2,6-dimethyl-phenyl)-acetonitrile as colourless solid: MS (EI): 163.1 (M+.), 148.1 ((M-CH3)+.), 136.1 ((M-HCN)+., 100%). to reflux for 4h The cooled reaction mixture was concentrated extracted with ethyl acetate The combined extracts were washed with brine dried over Na2SO4 filtered evaporated Filtration of the residue through a silica gel pad with heptane/ethyl acetate 1:1 provided (4-fluoro-2,6-dimethyl-phenyl)-acetonitrile as colourless solid

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

Procedure: A mixture of 3,5-dimethyl-fluorobenzene (5 g, 0.04 mol), paraformaldehyde (15 g), hydrobromic acid (70 ml) (30% in acetic acid) and acetic acid (25 ml) was stirred at ambient temperature for 4.5 h. To the mixture, water and petroleum ether were added and the organic layer was separated dried over anhydrous sodium sulfate and evaporated carefully under reduced pressure. The residue was purified by column chromatography on silica gel with petroleum ether as eluent to give the desired product. (3.7 g, 43%). the organic layer was separated dried over anhydrous sodium sulfate evaporated carefully under reduced pressure The residue was purified by column chromatography on silica gel with petroleum ether as eluent

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

Procedure: A mixture of 3,5-dimethyl-fluorobenzene (5 g, 0.04 mol), paraformaldehyde (15 g), hydrobromic acid (70 ml) (30% in acetic acid) and acetic acid (25 ml) was stirred at ambient temperature for 4.5 h. To the mixture were water and petroleum ether added and the organic layer was separated dried over anhydrous sodium sulfate and evaporated carefully under reduced pressure. The residue was purified by column chromatography on silica gel with petroleum ether as eluent to give the title product. (3.7 g, 43%) added the organic layer was separated dried over anhydrous sodium sulfate evaporated carefully under reduced pressure The residue was purified by column chromatography on silica gel with petroleum ether as eluent

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

Procedure: 4-hydroxy -2-methylbenzimidazole (0.57 g, 3.8 mmol) was dissolved in acetonitrile (4 ml). To the solution were added sodium hydroxide (0.17 g, 43 mmol) (dissolved in 1 ml water) and 2,6-dimethyl-4-fluorobenzylbromide (0.82 g, 3.8 mmol) dissolved in acetonitrile (6 ml) and the reaction mixture was refluxed for 80 min. and was stirred for 20 h. at ambient temperature. To the reaction mixture was added methylene chloride (25 ml) and water (25 ml). The organic layer was separated, washed three times with 2 M NaOH, dried over sodium sulfate and was evaporated under reduced pressure. The residue was crystallized from ethyl acetate and was then purified twice by column chromatography on silica gel a) methylene chloride: methanol (10:1) b) ethyl acetate: methanol:acetic acid: water (96:6:6:4). There was obtained 0.066 g (6%) of the title compound. the reaction mixture was refluxed for 80 min. The organic layer was separated washed three times with 2 M NaOH dried over sodium sulfate was evaporated under reduced pressure The residue was crystallized from ethyl acetate was then purified twice by column chromatography on silica gel a) methylene chloride: methanol (10:1) b) ethyl acetate: methanol:acetic acid: water (96:6:6:4)

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

Procedure: 4-hydroxy -2-methylbenzimidazole (0.57 g, 3.8 mmol) was dissolved in acetonitrile (4 ml). To the solution were added sodium hydroxide (0.17 g, 43 mmol) (dissolved in 1 ml water) and 2,6-dimethyl-4-fluorobenzylbromide (0.82 g, 3.8 mmol) dissolved in acetonitrile (6 ml) and the reaction mixture was refluxed for 80 min. and was stirred for 20 h. at ambient temperature. To the reaction mixture was added methylene chloride (25 ml) and water (25 ml). The organic layer was separated, washed three times with 2 M NaOH, dried over sodium sulfate and was evaporated under reduced pressure. The residue was crystallized from ethyl acetate and was then purified twice by column chromatography on silica gel a) methylene chloride: methanol (10:1) b) ethyl acetate: methanol:acetic acid: water (96:6:6:4). There was obtained 0.066 g (6%) of the title compound. the reaction mixture was refluxed for 80 min. The organic layer was separated washed three times with 2 M NaOH dried over sodium sulfate was evaporated under reduced pressure The residue was crystallized from ethyl acetate was then purified twice by column chromatography on silica gel a) methylene chloride: methanol (10:1) b) ethyl acetate: methanol:acetic acid: water (96:6:6:4)

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

Procedure: 8-Amino-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide mesylate (5.0 g, 13.4 mmol), 2,6-dimethyl-4-fluorobenzylbromide (2.91 g, 13.4 mmol), diisopropylethylamin (3.8 g, 29.5 mmol) and a cat. amount of potassium iodide were stirred in dimethylformamide (20 ml) at room temperature overnight. Water (70 ml) and methylene chloride (2×50 ml) were added to the reaction mixture and the organic layer was separated, dried and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using methylene chloride:methanol (9:1) as eluent. The product was solved in isopropanol and methansulfonic acid (0.3 g) was added. The salt that formed was isolated by filtration and washed with isopropanol and diethyl ether to give 1.4 g (24%) of the title compound. the organic layer was separated dried evaporated under reduced pressure The residue was purified by column chromatography on silica gel methansulfonic acid (0.3 g) was added The salt that formed was isolated by filtration washed with isopropanol and diethyl ether

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

Procedure: A solution of 1.86 g (9 mmol) 2,6-dimethyl-4-fluoro-benzyl bromide and 0.420 g (9 mmol) sodium cyanide in 21 ml ethanol/water 6:1 was heated to reflux for 4h. The cooled reaction mixture was concentrated and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. Filtration of the residue through a silica gel pad with heptane/ethyl acetate 1:1 provided (4-fluoro-2,6-dimethyl-phenyl)-acetonitrile as colourless solid: MS (EI): 163.1 (M+.), 148.1 ((M-CH3)+.), 136.1 ((M-HCN)+., 100%). to reflux for 4h The cooled reaction mixture was concentrated extracted with ethyl acetate The combined extracts were washed with brine dried over Na2SO4 filtered evaporated Filtration of the residue through a silica gel pad with heptane/ethyl acetate 1:1 provided (4-fluoro-2,6-dimethyl-phenyl)-acetonitrile as colourless solid