4-bromo-2-tert-butylaniline

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:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-bromo-2-tert-butylaniline (Reference Example 8, 25.0 g, 110 mmol) and bis(2-chloroethyl)amine hydrochloride (21.5 g, 120 mmol) in diethylene glycol dimethyl ether (157 mL) was stirred for 3 days at 170° C. It was cooled to room temperature, added 1 M sodium hydroxide solution (50 mL), and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give crude product. It was diluted with ethyl acetate and ether (50:50) and added 1 M hydrochloric acid solution to provide 1-(4-bromo-2-tert-butylphenyl)piperazine dihydrochloride (16.2 g, 40%) as a gray solid. It was cooled to room temperature extracted with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure to give crude product

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

Procedure: To a solution of 2-tert-butylaniline (50 g, 335 mmol) in THF (500 mL) was added tetrabutylammonium tribromide (234.5 g, 335 mmol) at 0° C. After the solution was stirred for 30 minutes at that temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated Na2S2O3 solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the crude product. The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=100:0 to 20:80) to provide 4-bromo-2-tert-butylaniline (74.6 g, 98%) as a pink oil. extracted with ethyl acetate The organic layer was washed with saturated Na2S2O3 solution and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure to give the crude product The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=100:0 to 20:80)

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

Procedure: To a solution of 2-tert-butylaniline (50 g, 335 mmol) in THF (500 mL) was added tetrabutylammonium tribromide (234.5 g, 335 mmol) at 0° C. After the solution was stirred for 30 minutes at that temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated Na2S2O3 solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the crude product. The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=100:0 to 20:80) to provide 4-bromo-2-tert-butylaniline (74.6 g, 98%) as a pink oil. extracted with ethyl acetate The organic layer was washed with saturated Na2S2O3 solution and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure to give the crude product The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=100:0 to 20:80)

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: To a solution of 2-tert-butylaniline (14.9 g, 100 mmol) was added a solution of NBS (17.8 g, 100 mmol) in DMF at rt. The reaction mixture was stirred for 1 h at rt, diluted with water (30 mL) and extracted with Et2O (3×250 mL). The organic layer was washed with brine, dried over Na2SO4, concentrated and purified by CC to give compound P25a (19 g, 83%). extracted with Et2O (3×250 mL) The organic layer was washed with brine dried over Na2SO4 concentrated purified by CC to give compound P25a (19 g, 83%)

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

Procedure: To a solution of NBS (218 mg, 1 mmol) in DMF was added a solution of 2-tert-butylaniline (149 mg, 1 mmol) in DMF at rt. The reaction mixture was stirred for 4 h at rt, then water (30 mL) was added and the mixture was extracted with EA (150 mL). The organic layer was washed with brine and dried over Na2SO4, concentrated and purified by CC (hexane/EA=3/1) to give compound P19a (180 mg, 79%). the mixture was extracted with EA (150 mL) The organic layer was washed with brine dried over Na2SO4 concentrated purified by CC (hexane/EA=3/1) to give compound P19a (180 mg, 79%)