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, 14.73 mmol) in DCM (120 ml) was added DIPEA (5.40 ml, 30.9 mmol) and then 4-(trifluoromethyl)benzenesulfonyl chloride (3.96 g, 16.20 mmol). The reaction mixture was stirred 2.5 hours at room temperature 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 aq. HCl in 1,4-dioxane (18.41 ml, 73.6 mmol) overnight. The mixture was concentrated under 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 aq. HCl (2×200 ml). 2M aq. NaOH solution was added to the 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 under 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 under 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 aq. HCl (2×200 ml)
12. addition2M aq. NaOH solution was added to the 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 under vacuo

ORD-Eintrag

ord-a35744ef925e4e3d906abb73e0363e80

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08536183B2