Trifluoroacetic acid → 2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)aniline

Participants

Reaction Conditions

Reaction Steps

Anisole (633 μl, 5.80 mmol) was added to a solution of tert-butyl (2-chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (312 mg, 0.58 mmol) in DCE (3 mL), followed by the addition 2.8 mL of TFA. The reaction was stirred at 60° C. for 3 h. The residue was partitioned between CH2Cl2 and sat. NaHCO3, and extracted into CH2Cl2 (3×). The solution was dried over Na2SO4 and concentrated. The residue was dissolved in MeOH and loaded onto a 5 g Strata SCX ion exchange cartridge, washing with MeOH. The desired product was eluted with 7 N NH3—CH3OH. After concentration, 163.4 mg of 2-chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)aniline was obtained.

Provenance & Evidence