Triethylamine → (R)-alpha-hexyl-4-nitro-1H-imidazole-1-acetic acid

Temperatur

80 °C

To a solution of (-)-cinchonidine (48.0 g, 163 mmol) in 880 mL of distilled H2O at room temperature was added 2-(4-nitro-1H-imidazol-1-yl)-octanoic acid (83.0 g, 326 mmol) as a solution in 440 mL of ethanol. To this mixture was added triethylamine (11.7 mL). The mixture was then heated to 80° C., and the pH was maintained between 6.9 and 7.1 by the dropwise addition of triethylamine (5-10 mL). After the pH stabilized at 7.01, the solution was allowed to cool to room temperature, and let stand overnight whereupon crystallization of the (R)-2-(4-nitro-1H-imidazol-1-yl)-octanoic acid-cinchonidine salt occurred. The crystalline salt was collected by filtration. The salt was then suspended in 200 mL ea. of ethyl acetate/H2O. To this suspension was added in HCl (750 mL). The layers were separated, and the aqueous was extracted with ethyl acetate (2×500 mL). The organic was combined, dried (Na2SO4 ), and concentrated in vacuo to provide 29.9 g (72%) of (R)-2-(4-nitro-1H-imidazol-1-yl)-octanoic acid as an off-white solid. M.pt. 116°-118° C. Calculated for C11H17N3O4 : C, 51.76; H, 6.71; N, 16.46. Found: C, 51.89; H, 6.76; N, 16.20. [a]D -29.9 (c 1.00, ethanol).

1. temperatureto cool to room temperature
2. customlet stand overnight whereupon crystallization of the (R)-2-(4-nitro-1H-imidazol-1-yl)-octanoic acid-cinchonidine salt
3. filtrationThe crystalline salt was collected by filtration
4. additionTo this suspension was added in HCl (750 mL)
5. customThe layers were separated
6. extractionthe aqueous was extracted with ethyl acetate (2×500 mL)
7. dry with materialdried (Na2SO4 )
8. concentrationconcentrated in vacuo

ORD-Eintrag

ord-269dd235cdde430e8f651e0152bf27f4

Quelldatensatz

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05484780