Hydrochloric Acid → 2-Fluoro-6-methylaniline

HRID 619968Notes

Reaction equation

HRID 619968 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])=O)(C)(C)C.[C:16]([Li])(C)(C)C.CI.Cl>C1COCC1.CCCCC>[F:15][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([CH3:16])[C:9]=1[NH2:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 4935500Tert-butyl 2-fluorophenylcarbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 141554112-Fluoro-6-methylanilineYield 80%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

A solution of 8.15 g (38.5 mmol) of N-t-butoxycarbonyl-2-fluoroaniline in 30 ml of dry THF was cooled 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 temperature 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, b.p. 91°-93° C. (0.1 mm). IR and 1H NMR spectra were in agreement with the assigned structure.

Workup

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

Sources & evidence

ORD record
ord-0e2a03064dce4aaebe8c6aba1d063989
Source dataset
uspto-grants-1989_04
Patent number
US04818273

Reaction notes

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