2,6-diethylbenzaldehyde

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:

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

Procedure: To a solution of 8.01 g (60 mmol) aluminum trichloride in 10 ml dichloromethane were added at ambient temperature drop-wise 5.52 g (34 mmol) 2,6-diethyl-benzaldehyde (Example 1 c)); exothermic reaction. To the resulting dark red solution was added slowly drop-wise a solution of 5.5 g (34 mmol) bromine in 7 ml dichloromethane; strong exothermic reaction. Then the mixture was heated to 40° C. for 3 hours. The reaction mixture was cooled to ambient temperature and poured onto ice. The organic phase was separated and the aqueous solution extracted with dichloromethane, the combined extracts washed with 2N HCl solution, saturated sodium bicarbonate solution and brine, dried over MgSO4, filtered and evaporated: 7.0 g 3-bromo-2,6-diethyl-benzaldehyde of 90% purity (HPLC) that did not require further purification. exothermic reaction strong exothermic reaction The reaction mixture was cooled to ambient temperature poured onto ice The organic phase was separated the aqueous solution extracted with dichloromethane the combined extracts washed with 2N HCl solution, saturated sodium bicarbonate solution and brine dried over MgSO4 filtered evaporated purification

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

Procedure: To a solution of 8.01 g (60 mmol) aluminum trichloride in 10 ml dichloromethane were added at ambient temperature drop-wise 5.52 g (34 mmol) 2,6-diethyl-benzaldehyde (Example 1 c)); exothermic reaction. To the resulting dark red solution was added slowly drop-wise a solution of 5.5 g (34 mmol) bromine in 7 ml dichloromethane; strong exothermic reaction. Then the mixture was heated to 40° C. for 3 hours. The reaction mixture was cooled to ambient temperature and poured onto ice. The organic phase was separated and the aqueous solution extracted with dichloromethane, the combined extracts washed with 2N HCl solution, saturated sodium bicarbonate solution and brine, dried over MgSO4, filtered and evaporated: 7.0 g 3-bromo-2,6-diethyl-benzaldehyde of 90% purity (HPLC) that did not require further purification. exothermic reaction strong exothermic reaction The reaction mixture was cooled to ambient temperature poured onto ice The organic phase was separated the aqueous solution extracted with dichloromethane the combined extracts washed with 2N HCl solution, saturated sodium bicarbonate solution and brine dried over MgSO4 filtered evaporated purification

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

Procedure: To a solution of 3.80 g (23.4 mmol) 2,6-diethyl-benzaldehyde and 12.3 g (47 mmol) triphenylphosphine in 100 ml dry dichloromethane cooled to −20° C. was added drop-wise a solution of 9.32 g (28.1 mmol) tetrabromomethane in 70 ml dichloromethane. The reaction temperature was kept below 5° C. After the addition the reaction mixture was kept at −10° C. for 5 minutes and then for 30 minutes at ambient temperature. The reaction mixture was poured onto water, extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent: 4.50 g 2-(2,2-dibromo-vinyl)-1,3-diethyl-benzene as colourless liquid: MS (EI): 319.9 and 318.0 and 316.0 (M+.), 239.1 and 237.1 ((M-Br)+.), 158.2 ((M-Br2)+., 100%). was kept below 5° C After the addition the reaction mixture for 30 minutes at ambient temperature The reaction mixture was poured onto water extracted with ethyl acetate the combined extracts washed with brine dried over Na2SO4 filtered evaporated The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent

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

Procedure: To a solution of 3.80 g (23.4 mmol) 2,6-diethyl-benzaldehyde and 12.3 g (47 mmol) triphenylphosphine in 100 ml dry dichloromethane cooled to −20° C. was added drop-wise a solution of 9.32 g (28.1 mmol) tetrabromomethane in 70 ml dichloromethane. The reaction temperature was kept below 5° C. After the addition the reaction mixture was kept at −10° C. for 5 minutes and then for 30 minutes at ambient temperature. The reaction mixture was poured onto water, extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent: 4.50 g 2-(2,2-dibromo-vinyl)-1,3-diethyl-benzene as colourless liquid: MS (EI): 319.9 and 318.0 and 316.0 (M+.), 239.1 and 237.1 ((M-Br)+.), 158.2 ((M-Br2)+., 100%). was kept below 5° C After the addition the reaction mixture for 30 minutes at ambient temperature The reaction mixture was poured onto water extracted with ethyl acetate the combined extracts washed with brine dried over Na2SO4 filtered evaporated The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent

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

Procedure: A solution of 15.6 g (E)-[1-(2,6-diethyl-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine in 60 ml THF and 120 ml 4N HCl was heated to reflux for 2 hours then cooled to ambient temperature and poured onto a 1N NaOH solution. The aqueous phase was extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent: 8.35 g 2,6-diethyl-benzaldehyde as light yellow oil: MS (EI): 162.1 (M+., 100%). to reflux for 2 hours The aqueous phase was extracted with ethyl acetate the combined extracts washed with brine dried over Na2SO4 filtered evaporated The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent

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

Procedure: A solution of 15.6 g (E)-[1-(2,6-diethyl-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine in 60 ml THF and 120 ml 4N HCl was heated to reflux for 2 hours then cooled to ambient temperature and poured onto a 1N NaOH solution. The aqueous phase was extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent: 8.35 g 2,6-diethyl-benzaldehyde as light yellow oil: MS (EI): 162.1 (M+., 100%). to reflux for 2 hours The aqueous phase was extracted with ethyl acetate the combined extracts washed with brine dried over Na2SO4 filtered evaporated The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent

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

Procedure: 4-Amino-2-methylbenzimidazole (0.79 g, 5.4 mmol) and 2,6-diethylbenzaldehyde (1.1 g, 6.6 mmol) were dissolved in methanol (30 ml). ZnCl2 (0.9 g, 6.6 mmol) and subsequently NaBH3CN (0.42 g, 6.6 mmol) in small portions were added and the mixture was refluxed under argon for 3 hours and was stirred at room temperature for 16 h. The mixture was poured over an aqueous 1M NaOH solution (50 ml). The resultant yellow suspension was extracted with DCM and the organic solution was washed with brine, dried over Na2SO4 and then evaporated under reduced pressure. The oily residue (1.8 g) was purified by crystallization from a mixture of ethyl acetate and acetonitrile to give 0.65 g (41%) of the title compound. the mixture was refluxed under argon for 3 hours The resultant yellow suspension was extracted with DCM the organic solution was washed with brine dried over Na2SO4 evaporated under reduced pressure The oily residue (1.8 g) was purified by crystallization from a mixture of ethyl acetate and acetonitrile