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

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).

1. washthen washed with water (250 ml)
2. customdried on a phase separation cartridge
3. concentrationconcentrated in vacuo
4. dissolutionThe obtained product was dissolved in 1,4-dioxane (60 ml)
5. concentrationThe mixture was concentrated in vacuo
6. dissolutionthen dissolved in EtOAc (150 ml)
7. washwashed with 2N aq. NaOH solution (200 ml)
8. customthen dried on a phase separation cartridge
9. concentrationconcentrated in vacuo
10. dissolutionThe product was then dissolved in EtOAc (100 ml)
11. extractionextracted with 2M HCl (2×200 ml)
12. addition2M NaOH solution were added to aqueous layer until basic pH
13. extractionthe product was extracted with EtOAc (500 ml)
14. customThe organic layer was dried on a phase separation cartridge
15. concentrationconcentrated in vacuo

ORD record

ord-0aa97d9c18c24885abae0f568cdfbed9

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093249B2