4-bromo-2-chloro-3,5-difluoroaniline

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

Procedure: A mixture of 4-bromo-2-chloro-3,5-difluoroaniline (5.35 g, 22.0 mmol), cyclopropylboronic acid (2.20 g, 24.0 mmol), K3PO4 (16 g, 78 mmol) and tricyclohexyl phosphine (0.623 g, 2.24 mmol) in toluene (30 mL) and water (8 mL) is degassed with N2 and heated to 100° C. Pd(OAc)2 (0.25 g, 1.16 mmol) is added. The reaction mixture is heated to 100° C. overnight, cooled and loaded directly on a column of silica gel. The residue is purified by column chromatography (EtOAc/hexanes) to give 4-cyclopropyl-3,5-difluoro-2-chloroaniline. is degassed with N2 The reaction mixture is heated to 100° C. overnight cooled The residue is purified by column chromatography (EtOAc/hexanes)

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

Procedure: 4-Bromo-3,5-difluoroaniline (10.5 g, 50.5 mmol) is dissolved in DMF (100 mL). NCS (28.6 g, 50.5 mmol) is added portionwise at room temperature. After 48 hours, the reaction is diluted with Et2O and washed with brine. The separated organic phase is dried (Na2SO4) and concentrated to give an oil. The residue is purified by column chromatography (EtOAc/hexanes) to give 4-bromo-2-chloro-3,5-difluoroaniline. washed with brine The separated organic phase is dried (Na2SO4) concentrated to give an oil The residue is purified by column chromatography (EtOAc/hexanes)