Isoamyl Nitrite → 2-Fluoro-3-methyl-1,1'-biphenyl

A stirred solution of 3-methyl-[1,1'-biphenyl]-2-amine (7.5 g, 0.041 mole, as prepared in method K) in 20 ml of tetrahydrofuran was cooled to 5°. A solution of 40 ml tetrafluoroboric acid (48-50% solution) in 20 ml of water was added to the cooled reaction mixture, followed by dropwise addition of isoamyl nitrite (6.2 g, 0.053 mole). After complete addition, the reaction mixture was stirred for 15 minutes and filtered. The filter cake was rinsed successively with 50 ml each of 5% aqueous tetrafluoroboric acid, cold methanol, and cold diethyl ether. The filter cake was added to 100 ml of toluene and the mixture stirred and heated at 60° until the solid dissolved and bubbling subsided. The mixture was heated at reflux for 30 minutes, then held at room temperature for two days, causing separation of an oil. The toluene was decanted from the oil and evaporated under reduced pressure to give a second oil, which was purified by column chromatography on silica gel, elution by toluene:n-heptane (6:94), to give 2-fluoro-3-methyl-[1,1'biphenyl].

1. additionAfter complete addition
2. filtrationfiltered
3. washThe filter cake was rinsed successively with 50 ml each of 5% aqueous tetrafluoroboric acid, cold methanol, and cold diethyl ether
4. additionThe filter cake was added to 100 ml of toluene
5. stirringthe mixture stirred
6. temperatureheated at 60° until the solid
7. dissolutiondissolved
8. custombubbling
9. temperatureThe mixture was heated
10. temperatureat reflux for 30 minutes
11. waitheld at room temperature for two days
12. customseparation of an oil
13. customThe toluene was decanted from the oil
14. customevaporated under reduced pressure
15. customto give a second oil, which
16. customwas purified by column chromatography on silica gel, elution by toluene:n-heptane (6:94)

ORD record

ord-7ed43473cd244642b92354b5728064f7

Source dataset

uspto-grants-1985_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04536591