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

Temperatur

50 °C

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).

1. temperatureAfter cooling to about 25° C.
2. customThe layers were separated
3. extractionthe aqueous extracted with ethyl acetate (15 ml)
4. washThe combined ethyl acetate layers were then washed with saturated brine (4×4 ml)
5. dry with materialdried with 2 g anhydrous sodium sulphate
6. concentrationthen concentrated under vacuum
7. temperatureThe residue was heated with acetonitrile (4 ml) to about 60° C.
8. customto give a solution
9. temperaturecooled to 0 to 5° C.
10. filtrationThe solid was filtered
11. washwashed with chilled acetonitrile (2 ml)
12. customdried at 40-45° C. under high vacuum

ORD-Eintrag

ord-c07866e3d5604193ada526fbbf9447f8

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08481566B2