Hydrochloric Acid → (3R)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl(2R)-2-methyl-1-piperazinecarboxylate (2.95 g, 14.7 mmol) in DCM (120 ml) was added DIPEA (5.40 ml, 30.9 mmol) and then 4-(trifluoromethyl)benzenesulfonyl chloride (3.96 g, 16.2 mmol). The reaction mixture was stirred 2.5 hours at rt then washed with water (250 ml), dried on a phase separation cartridge and concentrated in vacuo. The obtained product was dissolved in 1,4-dioxane (60 ml) and treated with 4M HCl in 1,4-dioxane (18.4 ml, 73.6 mmol) overnight. The mixture was concentrated in vacuo then dissolved in EtOAc (150 ml), washed with 2N aq. NaOH solution (200 ml) then dried on a phase separation cartridge and concentrated in vacuo. The product was then dissolved in EtOAc (100 ml) and extracted with 2M HCl (2×200 ml). 2M NaOH solution were added to aqueous layer until basic pH then the product was extracted with EtOAc (500 ml). The organic layer was dried on a phase separation cartridge and concentrated in vacuo to give the title compound (3.76 g).

Provenance & Evidence