Reaction #61684

Reaction equation

1,5-dibromo-3-fluoro-6-methoxy-5-nitrobenzene

N2

→

2-Fluoro-5-methoxyaniline

Yield 84.0%

Solvents

ethanol

Conditions

Workup

1. 1
   OtherThe stirred reaction mixture
2. 2
   Otherpurge
3. 3
   OtherThe reaction mixture was evacuated
4. 4
   OtherThe reaction mixture was evacuated
5. 5
   workup.ADDITIONH2 was introduced until a pressure of 7 bars
6. 6
   Temperatureto maintain the internal pressure at 7 bars (note that after 24 hours
7. 7
   Otherthe catalyst was removed by filtration through 2 glass microfibre pads under an atmosphere of N2
8. 8
   Concentrationthe filtrate was concentrated to dryness under reduced pressure at 45° C
9. 9
   workup.DISSOLUTIONThe resulting dark orange solid was dissolved in water (500 mL)
10. 10
    ExtractionThe resulting brown suspension was extracted with tert-butylmethylether (2×1 L)
11. 11
    WashThe combined organic extracts were washed with water (500 mL)
12. 12
    Dryingdried over sodium sulfate
13. 13
    Filtrationfiltered
14. 14
    Concentrationconcentrated in vacuo at 40° C.

Procedure

A 2.0 L pressure reactor was charged with 10% Pd/C (50% wet paste, 10 g). A solution of 1,5-dibromo-3-fluoro-6-methoxy-5-nitrobenzene (50 g, 0.152 mol) in ethanol (absolute grade, 1.5 L) was added to the catalyst under N2. The stirred reaction mixture was subjected to three cycles of vacuum followed by N2 purge. The reaction mixture was evacuated prior to the introduction of H2 at a pressure of 4 bars. The reaction mixture was evacuated and H2 was introduced until a pressure of 7 bars was reached. The reaction mixture was stirred at 25° C. for 48 hours, with periodic injections of H2 to maintain the internal pressure at 7 bars (note that after 24 hours, the catalyst was replaced). After the reaction had reached completion, the catalyst was removed by filtration through 2 glass microfibre pads under an atmosphere of N2 and the filtrate was concentrated to dryness under reduced pressure at 45° C. The resulting dark orange solid was dissolved in water (500 mL) and the pH of the resulting solution adjusted to >12 using aqueous NaOH (1N, 400 mL). The resulting brown suspension was extracted with tert-butylmethylether (2×1 L). The combined organic extracts were washed with water (500 mL), dried over sodium sulfate, filtered and concentrated in vacuo at 40° C. to afford 2-Fluoro-5-methoxyaniline (18.0 g, 84%) as a brown solid.

Source