5-Bromo-1,3-dihydro-benzo(c)thiophene 2,2-dioxide

150527-38-1

351005-12-4

1. 4-Bromo-1,2-bis(bromomethyl)benzene (3.42 g, 9.96 mmol) was dissolved in a 2:1 solvent mixture of ethanol (EtOH) and THF (1196 mL) and heated to 70 °C with stirring. 2. An aqueous solution (40 mL) of Na2S-9H2O (2.63 g, 10.96 mmol) was added dropwise over 10 hours using a syringe pump. Continue heating and stirring for 10 hours. 3. Cool to room temperature and remove the organic solvent under reduced pressure. Water (200 mL) was added to the residue and the aqueous layer was extracted with EtOAc (3 x 200 mL). The organic layers were combined, dried over Na2SO4, filtered, concentrated and purified by fast column chromatography (silica gel, hexane) to afford 5-bromo-1,3-dihydrobenzo[c]thiophene (1.27 g, 59%). 4. 5-Bromo-1,3-dihydrobenzo[c]thiophene (1.25 g, 5.79 mmol) was dissolved in methanol (25 mL) and potassium persulfate (10.7 g, 17.4 mmol) was added. 5. The reaction mixture was stirred at 0 °C for 2 h. 1 M aqueous sodium bisulfite solution (100 mL) was added and stirred for 10 min, then saturated NaHCO3 solution (200 mL) was added. 6. Extract the aqueous layer with CH2Cl2 (3 x 100mL). The organic layers were combined, dried over Na2SO4, filtered, concentrated, and purified by fast column chromatography (silica gel, 0-5% MeOH/CH2Cl2) to afford 5-bromo-1,3-dihydrobenzo[c]thiophene 2,2-dioxide (930 mg, 65%). 7. 5-bromo-1,3-dihydrobenzo[c]thiophene (860 mg, 3.50 mmol) and hexamethyldistannane (3 eq.) were dissolved in toluene and tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 0.1 eq.) was added. 8. The flask was rinsed with N2, heated to 120 °C with stirring, continued to heat for 5 h, and cooled to room temperature. 9. Water (50 mL) was added and the aqueous layer was extracted with EtOAc (3 x 50 mL). The organic layers were combined, dried over Na2SO4, filtered, concentrated, and purified by fast chromatography (silica gel, 10-30% EtOAc/hexane) to afford 5-bromo-1,3-dihydrobenzo[c]thiophene 2,2-dioxide (1.22 g, 100%).