Water → 1-(Methylsulfonyl)piperazine

Temperature

-20 °C

Methanesulphonyl chloride (18.3 mL, 0.236 mol) was added dropwise to a solution of tert-butyl piperazine-1-carboxylate (40 g, 0.214 mol) and triethylamine (60 mL, 0.43 mol) in CH2Cl2 (300 mL) in argon under stirring at −20° C. The mixture was stirred at room temperature for 1 h, and water (100 mL) was added. The layers were separated, and the water layer was extracted with chloroform (2×200 mL). The organic fraction were washed with the 1 N NaHSO4 solution (100 mL), the saturated NaHCO3 solution (100 mL), dried over Na2SO4, filtered through SiO2 (50 g, 40-63 μm), and evaporated to dryness. The residue (white crystals) was dissolved in isopropanol (200 mL), concentrated HCl (35 mL) was added, and the mixture was refluxed for 1 h and evaporated. Chloroform (200 mL), the saturated K2CO3 solution (50 mL), and water (50 mL) were added to the residue under stirring. The organic layer was separated, and the water layer was extracted with chloroform (2×100 mL). The organic layers were dried over Na2SO4, filtered through SiO2 (50 g, 40-63 μm), and evaporated to dryness. The residue (white crystals) was dried to give the title compound in 94% (33 g) yield. LCMS data: M+H 165.0 (Calculated for C5H12N2O2S 164.23), 97.2%, r.t. 0.913 min. 1H-NMR data (dmso-d6): 2.99 (m, 4H), 2.83 (s, 3H), 2.74 (m, 4H).

1. stirringThe mixture was stirred at room temperature for 1 h
2. customThe layers were separated
3. extractionthe water layer was extracted with chloroform (2×200 mL)
4. washThe organic fraction were washed with the 1 N NaHSO4 solution (100 mL)
5. dry with materialthe saturated NaHCO3 solution (100 mL), dried over Na2SO4
6. filtrationfiltered through SiO2 (50 g, 40-63 μm)
7. customevaporated to dryness
8. dissolutionThe residue (white crystals) was dissolved in isopropanol (200 mL)
9. additionconcentrated HCl (35 mL) was added
10. temperaturethe mixture was refluxed for 1 h
11. customevaporated
12. additionChloroform (200 mL), the saturated K2CO3 solution (50 mL), and water (50 mL) were added to the residue
13. stirringunder stirring
14. customThe organic layer was separated
15. extractionthe water layer was extracted with chloroform (2×100 mL)
16. dry with materialThe organic layers were dried over Na2SO4
17. filtrationfiltered through SiO2 (50 g, 40-63 μm)
18. customevaporated to dryness
19. customThe residue (white crystals) was dried

ORD record

ord-a8661c6e51064a3a83004f46d479ba5b

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812040B2