Acetic Acid → Benzofuran

Temperature

-20 °C

For furo[3,2-b]pyridine compounds of formula xii(a) the reaction may be performed by first reacting a furo[3,2-b]pyridine of formula xvi where R7 is amino or preferably nitro with bromine in acetic acid. The reaction is typically performed at about 50° C. for about 4 hours. After the bromination is substantially complete, the volatiles are then removed under reduced pressure and the residue is subjected to an extractive work-up under basic conditions. The resulting 3-bromofuro[3,2-b]pyridine in diethyl ether is then treated with an alkyl lithium, typically-n-butyl lithium, in the same solvent, below −100° C. to affect a metal-halogen exchange. After stirring at this temperature for about 1 hour, the reaction mixture is treated with an equivalent of an appropriate compound of formula xvii. Once the addition of the compound of formula xvii is complete, the reaction mixture is stirred below −78° C. for an additional 3 to 5 hours. It is critical, when R1 is hydrogen, to maintain the reaction mixture at this temperature to avoid equilibration of the anion to the 2-position of the benzofuran ring. The reaction mixture is then allowed to warm to −20° C. over about 50 minutes. An excess of an appropriate base, preferably sodium or potassium hydroxide, in a lower alkanol, typically methanol or ethanol is then added and the reaction refluxed for 0.25 to 24 hours to provide a benzofuran compound of formula xii(a) where R7 is amino or nitro.

1. customthe volatiles are then removed under reduced pressure
2. additionThe resulting 3-bromofuro[3,2-b]pyridine in diethyl ether is then treated with an alkyl lithium
3. customin the same solvent, below −100° C.
4. additionthe reaction mixture is treated with an equivalent of an appropriate compound of formula xvii
5. additionOnce the addition of the compound of formula xvii
6. stirringthe reaction mixture is stirred below −78° C. for an additional 3 to 5 hours
7. temperatureto maintain the reaction mixture at this temperature
8. additionAn excess of an appropriate base, preferably sodium or potassium hydroxide, in a lower alkanol, typically methanol or ethanol is then added
9. temperaturethe reaction refluxed for 0.25 to 24 hours

ORD record

ord-3ae85c1785da4e539bed11828c38ca6b

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06696439B1