Carbon Dioxide → HCID 13348264, compound

Participants

Reaction Conditions

Reaction Steps

A 2.5 M solution of n-BuLi (39.65 mL, 99.13 mmol) was added at −20° C. to a stirred solution of 14.8 g (90.12 mmol) of 6-methoxybenzo[b]thiophene (S. L. Grahm, et al. Topically Active Carbonic Anhydride Inhibitor. 2. Benzo[b]thiophenesulfonamide Derivatives with Ocular Hypotensive Activity. J. Med. Chem. 1989, 32 2548-2554) in 100 mL of anhydrous tetrahydrofuran with 5 mg of 2,2′-dipyridyl over 15 min. The resulting solution was stirred at −78° C. for 10 min and a tetrahydrofuran (100 mL) solution of ZnI2 (31.63 g, 99.12 mmol) was added during 30 min. After warming up to 0° C. for 5 min and cooling back to −78° C. p-toluenesulfonyl cyanide (17.15 g, 94.64 mmol) in tetrahydrofuran (100 mL) was added over a period of 30 min, and the reaction mixture was warmed to room temperature and stirred for 16 h. The mixture was quenched with NH4Cl solution (300 mL) and then extracted with Et2O (3×250 mL). The combined Et2O layers were washed with H2O, dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica-gel:450 g; hexane-EtOAc 95:5) to give 3.2 g (16%) of 6-methoxybenzo[b]thiophene-2-carbonitrile as a pink solid, mp 82-83° C. (Et2O).

Provenance & Evidence