* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With n-butyllithium; In tetrahydrofuran; N,N-dimethyl-formamide;
B. 4-Chloro-2,6-dimethyl benzaldehyde Dissolve <strong>[103724-99-8]4-bromo-3,5-dimethyl chlorobenzene</strong> (6.5 g) in 50 mL anhydrous THF and cool to -78 C. (dry ice/acetone) under N2. Dropwise over 5 minutes add a solution of butyllithium (12.50 mL, 2.5M in hexanes) to the stirring solution of aryl bromide at -78 C. After 2 hours, dropwise add anhydrous DMF (5.0 mL) to the orange/red reaction solution and allow to warn to ambient temperature overnight while stirring under N2. Evaporate the yellow solution down to a yellow oil and partition between H2O (100 mL) and CH2Cl2 (100 mL). Extract the aqueous layer once with CH2Cl2, then pool the organic layers and dry over Na2SO4, filter and evaporate down to 5.0 g of yellow oil. Use without further purification. LCMS=169.6 (MH+)
With n-butyllithium; In tetrahydrofuran; N,N-dimethyl-formamide;
B. 4-Chloro-2,6-dimethyl benzaldehyde Dissolve <strong>[103724-99-8]4-bromo-3,5-dimethyl chlorobenzene</strong> (6.5 g) in 50 mL anhydrous THF and cool to -78 C. (dry ice/acetone) under N2. Dropwise over 5 min add a solution of butyllithium (12.50 mL, 2.5M in hexanes) to the stirring solution of aryl bromide at -78 C. After 2 h, dropwise add anhydrous DMF (5.0 mL) to the orange/red reaction solution and allow to warn to ambient temperature overnight while stirring under N2. Evaporate the yellow solution down to a yellow oil and partition between H2O (100 mL) and CH2Cl2 (100 mL). Extract the aqueous layer once with CH2Cl2, then pool the organic layers and dry over Na2SO4, filter and evaporate down to 5.0 g of yellow oil. Use without further purification. LCMS=169.6 (MH+).
4-chloro-2,6-dimethylaniline hydrochloride[ No CAS ]
[ 103724-99-8 ]
Yield
Reaction Conditions
Operation in experiment
In dichloromethane;
A. 4-Bromo-3,5-dimethyl chlorobenzene Slurry 2,6-dimethyl-4chloroaniline hydrochloride (23g, 193.11 g/mol) in CH2Cl2 (100 ml) and wash with saturated NaHCO3 to generate the free base. Dry over Na2SO4, filter and evaporate down to a violet oil. Slurry up in 120 mL 6.0 N H2SO4 and stir vigorously at ambient temperature to break up larger pieces of solid.
In dichloromethane;
A. 4-Bromo-3,5-dimethyl chlorobenzene Slurry 2,6-dimethyl-4-chloroaniline hydrochloride (23 g, 193.11 g/mol) in CH2Cl2 (100 ml) and wash with saturated NaHCO3 to generate the free base. Dry over Na2SO4, filter and evaporate down to a violet oil. Slurry up in 120 mL 6.0 N H2SO4 and stir vigorously at ambient temperature to break up larger pieces of solid.
EXAMPLE 34-Chloro-2,6-dimethylbromobenzene; The procedure is as in Example 1, except that only 6.95 g [0.025 mol] of FeSO4×7H2O are used. This gives 20.7 g of an oil which, according to GC, contains 97.1% 4-chloro-2,6-dimethylbromobenzene (91% of theory).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 85℃; for 18h;Inert atmosphere; Sealed tube;
In a microwave vial equipped with a magnetic stirring bar and nitrogen flow at room temperature was placed <strong>[103724-99-8]2-bromo-5-chloro-1,3-dimethylbenzene</strong> (250 mg, 1.14 mmol), pinacol diborane (347 mg, 1.37 mmol), KOAc (335 mg, 3.42 mmol), and the catalyst PdCl2(dppf) (83 mg, 0.11 mmol). Nitrogen gas was bubbled through a solution of dioxane (5.7 mL) and then the solution was added to the reaction mixture. The vial was capped and placed in an oil bath at 85 C for 18 h. The reaction mixture was and filtered on a pad of Celite and washed with dioxane.The solvent was evaporated under vacuum and the crude product was purified by flash chromatography on silica gel using a solution of EtOAc in hexanes (1 to 2 % gradient) and afforded the title compound (94 mg, 0.35 mmol, 31%) as white solid.
31%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 20 - 85℃; for 18h;Inert atmosphere; Sealed tube;
In a microwave vial equipped with a magnetic stirring bar and nitrogen flow at room temperature was placed <strong>[103724-99-8]2-bromo-5-chloro-1,3-dimethylbenzene</strong> (250 mg, 1.14 mmol), pinacol diborane (347 mg, 1.37 mmol), KOAc (335 mg, 3.42 mmol), and the catalyst Pd012(dppf) (83 mg, 0.11 mmol). Nitrogen gas was bubbled through a solution of dioxane (5.7 mL) and then the solution was added to the reaction mixture. The vial was capped and placed in an oil bath at 85 00 for 18 h. The reaction mixture was and filtered on a pad of Celite and washed with dioxane.The solvent was evaporated under vacuum and the crude product was purified by flash chromatography on silica gel using a solution of EtOAc in hexanes (ito 2 % gradient) and afforded the title compound (94 mg, 0.35 mmol, 31%) as white solid.
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