Reaction SMILES: Cl.Cl.[Cl:3][CH2:4][CH2:5][CH2:6][N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.C(N(CC)CC)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22].Cl>C(Cl)Cl>[ClH:3].[Cl:3][CH2:4][CH2:5][CH2:6][N:7]1[CH2:12][CH2:11][N:10]([S:21]([CH3:20])(=[O:23])=[O:22])[CH2:9][CH2:8]1
Reactant: ClCCCN1CCNCC1
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCN(CCCCl)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 119.1 %

Procedure:
Step 1. To a suspension of 1-(3-chloropropyl)piperazine dihydrochloride (2.0 g, 8.18 mmol) in CH2Cl2 (50 ml) at 0° C. was added dropwise triethylamine (11.4 ml, 81.8 mmol) followed by a solution of methanesulfonyl chloride (0.8 ml, 9.81 mmol) in CH2Cl2 (10 ml). The reaction mixture was stirred at rt overnight and quenched with water. The organic layer was washed with water (3×25 ml), dried over MgSO4, and filtered. After removal of the solvent under vacuum, the residue was dissolved in ether (50 ml) and ethereal HCl (6.0 ml, 1M in ether, 6.0 mmol) was added dropwise at 0° C. The resulting precipitate was filtered, washed with ether (3×10 ml), and dried at 40° C. to afford 1-(3-chloropropyl)-4-(methanesulfonyl)piperazine hydrochloride (1.35 g, 60%). 1H NMR (500 MHz, DMSO-d6) δ 2.18-2.26 (m, 2H), 3.00 (s, 3H), 3.04-3.18 (m, 2H), 3.18-3.23 (m, 2H), 3.32 (t, J=12.2 Hz, 2H), 3.55-3.58 (m, 2H), 3.67-3.69 (m, 2H), 3.76 (t, J=6.4 Hz, 2H), 11.6 (brs, 1H). Step 2. To a solution of OZ288 (0.50 g, 1.4 mmol) in dry acetonitrile (50 ml) were added powdered NaOH (0.225 g, 5.61 mmol) and tetrabutylammonium hydrogensulfate (0.095 g, 0.28 mmol). After the reaction mixture was stirred at rt for 30 min, 1-(3-chloropropyl)-4-(methanesulfonyl)piperazine hydrochloride (0.39 g, 1.4 mmol) was added. The reaction mixture was stirred at 60° C. overnight and cooled to rt. The inorganic solid was filtered off and washed with EtOAc (2×25 ml). After removal of the solvents under vacuum, the residue was dissolved in EtOAc (50 ml). The organic layer was washed with water and brine, dried over MgSO4, filtered, and concentrated. The residue was purified by chromatography (silica gel, 50% EtOH in EtOAc) to afford the free base (0.17 g, 22%) as a colorless solid. To a solution of the above free base (0.17 g, 0.30 mmol) in EtOAc (10 ml) at 0° C. was added dropwise a solution of p-toluenesulfonic acid monohydrate (0.060 g, 0.30 mmol) in ether (10 ml). The resulting precipitate was filtered, washed with ether (25 ml), and dried under vacuum at 40° C. to afford trioxolane OZ482 (0.20 g, 88%) as a colorless solid. mp 148-150° C.; 1H NMR (500 MHz, DMSO-d6) δ 1.48-1.59 (m, 2H), 1.62-1.96 (m, 20H), 2.06-2.15 (m, 2H), 2.29 (s, 3H), 2.51-2.59 (m, 1H), 3.02 (s, 3H), 3.05-3.21 (m, 4H), 3.26-3.36 (m, 2H), 3.59-3.78 (m, 4H), 4.01 (t, J=5.8 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 7.12 (d, J=7.8 Hz, 2H), 7.13 (d, J=8.3 Hz, 2H), 7.49 (d, J=7.8 Hz, 2H), 9.51 (brs, 1H); 13C NMR (125.7 MHz, DMSO-d6) δ 20.95, 23.69, 25.98, 26.39, 31.48, 34.26, 34.43, 35.27, 35.96, 36.25, 40.86, 42.70, 50.77, 53.32, 64.82, 108.30, 110.72, 114.59, 125.66, 127.65, 128.27, 137.89, 138.49, 145.72, 156.64. Anal. Calcd for C37H52N2O9S2: C, 60.63; H, 7.15; N, 3.82. Found: C, 60.50; H, 7.31; N, 3.40.