Reaktion #534974

Reaktionsgleichung

1,3-difluoro-5-methyl-2-nitrobenzene

1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine, dihydrochloride

sodium bicarbonate

ethyl acetate

→

title compound

Ausbeute 42.6%

N-(3-fluoro-5-methyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine

Ausbeute 42.6%

Lösungsmittel

NMP

brine

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to about 25° C.
2. 2
   SonstigeThe layers were separated
3. 3
   Extraktionthe aqueous extracted with ethyl acetate (15 ml)
4. 4
   WaschenThe combined ethyl acetate layers were then washed with saturated brine (4×4 ml)
5. 5
   Trocknendried with 2 g anhydrous sodium sulphate
6. 6
   Einengenthen concentrated under vacuum
7. 7
   TemperaturThe residue was heated with acetonitrile (4 ml) to about 60° C.
8. 8
   Sonstigeto give a solution
9. 9
   Temperaturcooled to 0 to 5° C.
10. 10
    FiltrationThe solid was filtered
11. 11
    Waschenwashed with chilled acetonitrile (2 ml)
12. 12
    Sonstigedried at 40-45° C. under high vacuum

Vorschrift

A mixture of 1,3-difluoro-5-methyl-2-nitrobenzene (1 g), 1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine, dihydrochloride (1.63 g), sodium bicarbonate (1.94 g) and tetrabutyl ammonium iodide (100 mg) in NMP (15 ml) was slowly heated at about 50° C. for 3 hours. After cooling to about 25° C., the reaction mixture was added to ethyl acetate (15 ml) and saturated brine (15 ml). The layers were separated and the aqueous extracted with ethyl acetate (15 ml). The combined ethyl acetate layers were then washed with saturated brine (4×4 ml), dried with 2 g anhydrous sodium sulphate then concentrated under vacuum. The residue was heated with acetonitrile (4 ml) to about 60° C. to give a solution, then cooled to 0 to 5° C. and stirred for 1 hour. The solid was filtered, washed with chilled acetonitrile (2 ml), then dried at 40-45° C. under high vacuum to give the title compound as an orange solid (0.83 g).

Quelle