2-bromo-5-chloro-1,3-dimethylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Dissolve 4-bromo-3,5-dimethyl chlorobenzene (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+). to warn to ambient temperature overnight Evaporate the yellow solution down to a yellow oil partition between H2O (100 mL) and CH2Cl2 (100 mL) Extract the aqueous layer once with CH2Cl2 dry over Na2SO4 filter evaporate down to 5.0 g of yellow oil Use without further purification

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

Procedure: Dissolve 4-bromo-3,5-dimethyl chlorobenzene (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+) to warn to ambient temperature overnight Evaporate the yellow solution down to a yellow oil partition between H2O (100 mL) and CH2Cl2 (100 mL) Extract the aqueous layer once with CH2Cl2 dry over Na2SO4 filter evaporate down to 5.0 g of yellow oil Use without further purification

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an initial charge of 75 ml of 48% aqueous HBr are added, in portions, 19.67 g [0.12 mol] of 4-chloro-2,6-dimethylaniline. The resulting thick suspension is stirred at 80° C. for 15 minutes. Then the mixture is cooled to −10° C., and a solution of 9.6 g [0.139 mol] of NaNO2 in 45 ml of water is added dropwise within approx. 1 h at such a rate that the temperature does not exceed −5° C. 100 mg of sulphamic acid are added. Then the suspension of the diazonium salt, cooled to −10° C., is metered within about 35 minutes into a solution, heated to 80° C., of 17.93 g [0.125 mol] of Cu(I)Br in 75 ml of 62% aqueous HBr. The reaction mixture is then stirred at 80° C. for another 1 hour, allowed to cool to room temperature and admixed with 125 ml of water, the phases are separated and the aqueous phase is extracted three times with 50 ml each time of methylene chloride. The combined organic phases are washed twice with 25 ml each time of water, dried and concentrated under reduced pressure. This gives 20.2 g of an oil which, according to GC, contains 95.5% 4-chloro-2,6-dimethylbromobenzene (73% of theory). Then the mixture is cooled to −10° C. does not exceed −5° C cooled to −10° C. is metered within about 35 minutes into a solution The reaction mixture is then stirred at 80° C. for another 1 hour to cool to room temperature the phases are separated the aqueous phase is extracted three times with 50 ml each time of methylene chloride The combined organic phases are washed twice with 25 ml each time of water dried concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an initial charge of 65 ml of 48% aqueous HBr are added, in portions, 15.56 g [0.1 mol] of 4-chloro-2,6-dimethylaniline. The resulting thick suspension is stirred at 80° C. for 15 minutes. It is then cooled to −10° C., and a solution of 8 g [0.116 mol] of NaNO2 in 35 ml of water is added dropwise within approx. 40 minutes at such a rate that the temperature does not exceed −5° C. 80 mg of sulphamic acid are added. Then the suspension of the diazonium salt cooled to −10° C. is metered within about 25 minutes into a solution, heated to 80° C., of 28.6 g [0.103 mol] of FeSO4×7H20 in 65 ml of 62% aqueous HBr. The reaction mixture is then stirred at 80° C. for another 1 hour, allowed to cool to room temperature and admixed with 125 ml of water, the phases are separated and the aqueous phase is extracted three times with 50 ml each time of methylene chloride. The combined organic phases are washed twice with 25 ml each time of water, dried and concentrated under reduced pressure. This gives 17.2 g of an oil which, according to GC, contains 95.6% 4-chloro-2,6-dimethylbromobenzene (75% of theory). It is then cooled to −10° C. does not exceed −5° C cooled to −10° C. is metered within about 25 minutes into a solution The reaction mixture is then stirred at 80° C. for another 1 hour to cool to room temperature the phases are separated the aqueous phase is extracted three times with 50 ml each time of methylene chloride The combined organic phases are washed twice with 25 ml each time of water dried concentrated under reduced pressure

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

Procedure: Dissolve 4-bromo-3,5-dimethyl chlorobenzene (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+). to warn to ambient temperature overnight Evaporate the yellow solution down to a yellow oil partition between H2O (100 mL) and CH2Cl2 (100 mL) Extract the aqueous layer once with CH2Cl2 dry over Na2SO4 filter evaporate down to 5.0 g of yellow oil Use without further purification

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

Procedure: Dissolve 4-bromo-3,5-dimethyl chlorobenzene (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+) to warn to ambient temperature overnight Evaporate the yellow solution down to a yellow oil partition between H2O (100 mL) and CH2Cl2 (100 mL) Extract the aqueous layer once with CH2Cl2 dry over Na2SO4 filter evaporate down to 5.0 g of yellow oil Use without further purification

Conditions: temp:0.00; pressure:0.00; stir: