Methanesulfonyl Chloride

• Methansulfonyl Chloride (= MsCl) [M0094]
• Diethylene Glycol Monobenzyl Ether [D3408]
• Triethylamine (= TEA) [T0424]
• Dichloromethane

Triethylamine (1.64 mL, 10.2 mmol, 2.0 eq.) and MsCl (0.63 mL, 8.15 mmol, 1.6 eq.) were added to a solution of diethylene glycol monobenzyl ether (1.00 g, 5.10 mmol) in dichloromethane (7.3 mL) at room temperature. The reaction mixture was stirred for overnight. Additional triethylamine (1.64 mL, 10.2 mmol, 2.0 eq.) and MsCl (0.63 mL, 8.15 mmol, 1.6 eq.) were added and stirred for overnight. The reaction mixture was quenched with 1 mol/L HCl (10 mL) and extracted with dichloromethane (3 x 10 mL). The organic layer was washed with sat. NaHCO₃ aq. and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane = 10:90 – 50:50 on silica gel), giving 1 as a colorless liquid (1.57 g, >99% yield).

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 2:1, Rf = 0.6).

Compound 1

¹H NMR (270 MHz, DMSO-d₆); δ 7.38-7.25 (m, 5H), 4.49 (s, 2H), 4.32 (m, 2H), 3.68 (m, 2H), 3.64-3.61 (m, 2H), 3.58-3.57 (m, 2H), 3.17 (s, 3H).

• A MedChem toolbox for cereblon-directed PROTACs
• C. Steinebach, I. Sosič, S. Lindner, A. Bricelj, F. Kohl, Y. L. D. Ng, M. Monschke, K. G. Wagner, J. Krönke, M. Gütschow, MedChemComm 2019, 10, 1037.