Phosphorus pentachloride → 3-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)propane-1-sulfonyl chloride

Participants

Reaction Steps

Adapting a procedure according to Shue et al., Bioorg. Med. Chem. 1996, 6, 1709-1714, a 250 mL round-bottomed flask equipped with a magnetic stirring bar and a reflux condenser was charged under an atmosphere of nitrogen with 5.4 g (20 mmol) of potassium 3-(1,3-dioxobenzo[c]azolin-2-yl)propanesulfonic acid (10a), 150 mL of anhydrous dichloromethane (DCM), and 4.6 g (22 mmol) of phosphorus pentachloride (PCl5). The reaction mixture was heated to reflux. After reacting overnight, the reaction mixture was quenched with water and the phases were separated. The aqueous phase was extracted with dichloromethane (DCM). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and the solvents removed under reduced pressure using a rotary evaporator. After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent to provide 2.0 g (35% yield) of the title compound (10) as an off-white to beige solid. 1H NMR (400 MHz, CDCl3): δ=2.42-2.49 (m, 2H), 3.75-3.79 (m, 2H), 3.91 (t, J=6.4 Hz, 2H), 7.75-7.77 (m, 2H), 7.87-7.89 (m, 2H) ppm. MS (ESI) m/z 287.99 (M+H)+. The analytical data was consistent the proposed structure.

Provenance & Evidence