Hydrochloric Acid → 4-Benzyloxy-2-iodo-5-methoxybenzonitrile

Temperature

0 °C

To a mixture of 4-benzyloxy-2-iodo-5-methoxybenzamide (reference example 6-3) (5.25 g) and dichloromethane (70 mL) were added triethylamine (8.2 mL) and trifluoromethanesulfonic anhydride (4.6 mL) at 0° C. The mixture was stirred at 0° C. for 20 minutes, at room temperature for 3.5 hours and at reflux temperature for an hour. After cooling to 0° C., to the mixture were added triethylamine (4 mL) and trifluoromethanesulfonic anhydride (2.3 mL). After stirring at room temperature overnight, to the mixture were added ice-water and 1 mol/L hydrochloric acid. The mixture was extracted with ethyl acetate. The organic layer was washed with 1 mol/L hydrochloric acid and brine successively, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. A mixture of the residue, ethyl acetate, dichloromethane, silicagel and aminopropylsilicagel was stirred for 30 minutes. The mixture was passed through a layer of Celite (registered mark). The filtrate was concentrated under reduced pressure. The residue was triturated with methanol to give the title compound (3.72 g).

1. temperatureat reflux temperature for an hour
2. temperatureAfter cooling to 0° C., to the mixture
3. stirringAfter stirring at room temperature overnight, to the mixture
4. extractionThe mixture was extracted with ethyl acetate
5. washThe organic layer was washed with 1 mol/L hydrochloric acid and brine successively
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. additionA mixture of the residue, ethyl acetate, dichloromethane, silicagel and aminopropylsilicagel
9. stirringwas stirred for 30 minutes
10. concentrationThe filtrate was concentrated under reduced pressure
11. customThe residue was triturated with methanol

ORD record

ord-629f6dc77cbb4ed190121eb62d494c8f

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258162B2