4-Chlorobenzenesulfonyl chloride → Methyl 2-(3-chloro-4-(6-(4-chlorophenylsulfonamido)-1,3-dioxoisoindolin-5-yloxy)phenyl)acetate

Participants

Reaction Steps

Compound 30.2 (25 mg, 0.07 mmol) and 4-chlorobenzenesulfonyl chloride (30 mg, 0.14 mmol) were stirred in dichloromethane (0.5 mL) with 2,6-lutidine (0.25 mL, 0.21 mmol) at 25° C. for 14 h. The reaction mixture was loaded directly on a silica gel column and purified using 20% EtOAc/hexane as the eluent to give methyl 2-(3-chloro-4-(6-(4-chlorophenylsulfonamido)-1,3-dioxoisoindolin-5-yloxy)phenyl)acetate, and a compound with LC-MS matching a bis-sulfonamide. Both acetates were hydrolyzed in MeOH/THF/water (0.3 mL each) with LiOH.H2O (6 mg, 0.14 mmol) at 25° C. for 2 h to give the same desired product (30). The reaction mixtures were acidified to pH ˜3 and extracted with dichloromethane to give compound 30 as a pale-yellow solid. MS ESI (pos.) m/e calcd for (M+H3O)+ 539.0. found 539.0. 1H NMR (500 MHz) (DMSO-d6) δ 12.46 (br. s, 1H); 10.42 (s, 1H); 7.79 (d, J=8.3 Hz, 2H); 7.64 (d, J=8.5 Hz, 2H); 7.50 (d, J=1.9 Hz, 1H); 7.24 (dd, J=11.9, 8.3 Hz, 1H); 7.18 (s, 1H); 7.08 (s, 1H); 6.98 (s, 1H); 6.81 (d, J=8.2 Hz, 1H); 3.64 (s, 2H).

Provenance & Evidence