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

To a solution of 1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate (2.00 g, 9.99 mmol) in DCM (200 ml) was added DIPEA (3.66 ml, 20.97 mmol) and then 4-[(trifluoromethyl)oxy]benzenesulfonyl chloride (1.69 ml, 9.99 mmol) and the resulting mixture stirred at room temperature for 90 min. The reaction mixture was then concentrated under vacuum and re-dissolved in 1,4-dioxane (100 ml). A 4M solution of HCl in 1,4-dioxane (100 ml, 400 mmol) and a few drops of distilled water were added and the mixture stirred for 3 h. The reaction mixture was concentrated under vacuum, re-dissolved in DCM (200 ml) and washed with 2M aqueous NaOH (2×50 ml). The organic layer was dried (MgSO4), filtered and concentrated under vacuum. The residue was dissolved in ether and concentrated under vacuum. The oil was dissolved in MeOH (150 ml), applied to an SCX cartridge (50 g), which was washed with MeOH, DCM and MeOH again. The product was eluted from the column with 2M ammonia in methanol, DCM and then 2M ammonia in methanol; concentration under vacuum gave the title compound as a yellow transparent oil (2.92 g).

1. concentrationThe reaction mixture was then concentrated under vacuum
2. dissolutionre-dissolved in 1,4-dioxane (100 ml)
3. concentrationThe reaction mixture was concentrated under vacuum
4. dissolutionre-dissolved in DCM (200 ml)
5. washwashed with 2M aqueous NaOH (2×50 ml)
6. dry with materialThe organic layer was dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. dissolutionThe residue was dissolved in ether
10. concentrationconcentrated under vacuum
11. dissolutionThe oil was dissolved in MeOH (150 ml)
12. washwas washed with MeOH, DCM and MeOH again
13. washThe product was eluted from the column with 2M ammonia in methanol, DCM
14. concentrationconcentration under vacuum

ORD record

ord-d41602f4c1a04de3a26656e1028bf666

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536183B2