Hydrochloric Acid → 4-Cyano-7-methoxy benzo[b]thiophene

Temperature

150 °C

To a stirred solution of 4-bromo-7-methoxy benzo[b]thiophene (1.05 g, 4.32 mmol, 1 equiv.) in dry DMF (40 mL) was added copper(I)cyanide (3.885 g, 43.4 mmol, 10 equiv.) and the reaction mixture was heated at 150° C. overnight. The reaction mixture was cooled to ˜120° C. and then solid iron(III)chloride (1.58 g, 9.74 mmol) was added followed by 1 N HCl (CAUTION: HCN evolution—perform in a well vented hood!) The reaction mixture was heated at ˜100° C. for 2 hr before cooling to room temperature. Water, brine, and ethyl acetate were added and the layers were separated. The organic layer was washed with brine (3 times), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue thus obtained was purified via medium pressure liquid chromatography eluting with 10% ethyl acetate/90% hexanes to afford the title compound (564 mg, 69%) as a colorless solid; □H (400 MHz, CDCl3) 4.06 (3H, s), 6.81 (1H, d, J=8 Hz), 7.56 (1H, d, J=6 Hz), 7.65 (1H, d, J=6 Hz), 7.71 (1H, d, J=8 Hz).

1. temperatureThe reaction mixture was cooled to ˜120° C.
2. temperature) The reaction mixture was heated at ˜100° C. for 2 hr
3. temperaturebefore cooling to room temperature
4. customthe layers were separated
5. washThe organic layer was washed with brine (3 times)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude residue thus obtained
10. customwas purified via medium pressure liquid chromatography
11. washeluting with 10% ethyl acetate/90% hexanes

ORD record

ord-35b3613bc9bd47e59e048c3e3efd0461

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07037932B2