Hydrochloric Acid → HCID 86694695, compound

Temperature

40 °C

To a solution of tert-butyl 4-ethyl-5-nitro-1H-benzo[d]imidazole-1-carboxylate (13.6 g, 0.052 mol) in dry DCM (140 mL) was added TFA (20 mL, 0.26 mol, 5.0 equiv.), and the reaction mixture was heated at 40° C. for 16 h. The reaction mixture was concentrated and the crude solid re-dissolved in an acetone and water mixture (1:1, 40 mL). Concentrated HCl (14 mL) and sodium nitrite (3.95 g, 0.057 mol, 1.1 eq.) were then added at 0° C., and the reaction mixture was stirred at the same temperature for 30 min. The resulting solution was added dropwise to a solution of sodium cyanide (10.21 g, 0.21 mol, 4 equiv.) and CuCN (10.5 g, 0.084 mol, 1.6 equiv.) in an EtOAc and water mixture (1:1, 40 ml) at 0° C. The reaction mixture was then warmed to RT and stirred for a further 2 h. The reaction mixture was quenched with water and extracted with EtOAc. The combined organic layers were washed with brine then dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with 25% EtOAc/hexane to afford 4-ethyl-1H-benzo[d]imidazole-5-carbonitrile (6.8 g, 76% yield) as a yellow solid.

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe crude solid re-dissolved in an acetone and water mixture (1:1, 40 mL)
3. temperatureThe reaction mixture was then warmed to RT
4. stirringstirred for a further 2 h
5. customThe reaction mixture was quenched with water
6. extractionextracted with EtOAc
7. washThe combined organic layers were washed with brine
8. dry with materialthen dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by SiO2 chromatography
12. washeluting with 25% EtOAc/hexane

ORD record

ord-6cd4caae45db4b9084b612b053470b2d

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637537B2