Hydrochloric Acid → 2-Fluoro-6-methylaniline

Temperature

-70 °C

A solution of 8.15 g (38.5 mmol) of N-t-butoxycarbonyl-2-fluoroaniline in 30 ml of dry THF was coled to -70° C., and 46.3 ml (93 mmol) of 2.0M t-butyllithium in pentane was added dropwise at a rate sufficient to maintain the temperature below -65° C. When the addition was complete the reaction mixture was stirred at -70° C. for 15 minutes, warmed to -20° C. and stirred for 2.5 hours. A solution of 6.8 g (30 mmol) of methyl iodide in THF was added and the reaction was allowed to warm to room temperature. The reaction mixture was partitioned between ether and water, and the organic layer was washed with saturated aqueous NaCl and dried (MgSO4). Evaporation at reduced pressure gave a yellow solid which was added to 25 ml of 3N HCl and heated at reflux for 3 hours. After cooling to room the pH of the solution was adjusted to pH 7, and the solution was extracted twice with methylene chloride. The combined organic phases were washed with water and dried (MgSO4). Evaporation at reduced pressure gave a yellow oil which was Kugelrohr distilled to yield 3.8 g (80%) of the desired product as a liquid, bp 91°-93° C. (0.1 mm). IR and 1H NMR spectra were in agreement with the assigned structure.

1. customwas coled to -70° C.
2. temperatureto maintain the temperature below -65° C
3. additionWhen the addition
4. temperaturewarmed to -20° C.
5. stirringstirred for 2.5 hours
6. temperatureto warm to room temperature
7. customThe reaction mixture was partitioned between ether and water
8. washthe organic layer was washed with saturated aqueous NaCl
9. dry with materialdried (MgSO4)
10. customEvaporation at reduced pressure
11. customgave a yellow solid which
12. temperatureheated
13. temperatureat reflux for 3 hours
14. temperatureAfter cooling to room the pH of the solution
15. extractionthe solution was extracted twice with methylene chloride
16. washThe combined organic phases were washed with water
17. dry with materialdried (MgSO4)
18. customEvaporation at reduced pressure
19. customgave a yellow oil which
20. distillationdistilled

ORD record

ord-6c76c59ac333405bb09bc9e585f4f10d

Source dataset

uspto-grants-1988_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04741764