1-(Ethylsulfonyl)piperazine hydrochloride synthesis

Yield:859525-16-9 94%

Reaction Conditions:

with hydrogenchloride in 1,4-dioxane;dichloromethane at 20; for 15 h;

Steps:

2

Commercial 1-Boc-piperazine (Compound 5) (3.0 g, 16.11 mmol) was dissolved in methylene chloride (30 mL), then to the reaction mixture, which was stirred at -40 °C, were added triethylamine (5.61 mL, 40.28 mmol) and ethane sulfonyl chloride (1.83 mL, 19.33 mmol). The whole mixture was warmed up gradually and stirred for 14 hours. The whole mixture was poured into water and extracted with ethyl acetate. The organic layer of the extract was washed with dilute hydrochloric acid and saturated saline successively, then dried with sodium sulfate. The solvent was removed under reduced pressure and the residue was purified with silica-gel column chromatography to give ethane sulfonyl derivative (Compound 6) (3.82 g, 85%). Compound 6 (3.82 g, 13.72 mmol) was dissolved in the mixed solvent made of dioxane (5 mL) and methylene chloride (5 mL), then to the redaction mixture, which was stirred at room temperature, was added 4N hydrochloric acid (dioxane solvent) (8.58 mL, 34.31 mmol). The whole mixture was stirred at room temperature for 15 hours, then the resulting crystallized solid was filtered to give Compound 7 (2.76 g, 94%). ¹H-NMR (DMSO-d₆) δ: 1.22 (t, 3H, J= 7.2 Hz), 3.06-3.22 (m, 6H), 3.414-3.3.52 (m,4H), 9.59 (brs, 1H).

References:

EP2058305,2009,A1 Location in patent:Page/Page column 16