Reacción #567898

Ecuación de reacción

Carbonic Anhydride

n-BuLi

6-methoxybenzo[b]thiophene

p-toluenesulfonyl cyanide

Benzo[b]thiophenesulfonamide

→

6-methoxybenzo[b]thiophene-2-carbonitrile

Rendimiento 18.8%

Disolventes

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter warming up to 0° C. for 5 min
2. 2
   workup.ADDITIONwas added over a period of 30 min
3. 3
   Temperaturathe reaction mixture was warmed to room temperature
4. 4
   workup.STIRRINGstirred for 16 h
5. 5
   OtroThe mixture was quenched with NH4Cl solution (300 mL)
6. 6
   Extracciónextracted with Et2O (3×250 mL)
7. 7
   LavadoThe combined Et2O layers were washed with H2O
8. 8
   Secadodried (Na2SO4)
9. 9
   Otroevaporated in vacuo
10. 10
    OtroThe residue was purified by flash chromatography (silica-gel:450 g; hexane-EtOAc 95:5)

Procedimiento

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).

Fuente