Hydrochloric Acid → 1-Phenyl-1H-imidazo[4,5-c]pyridine-2-carbaldehyde

HRID 243040Notes

Reaction equation

C([Li])CCC.[C:6]1([N:12]2[C:20]3[CH:19]=[CH:18][N:17]=[CH:16][C:15]=3[N:14]=[CH:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CN([CH:24]=[O:25])C.Cl.C([O-])(O)=O.[Na+]>C1COCC1>[C:6]1([N:12]2[C:20]3[CH:19]=[CH:18][N:17]=[CH:16][C:15]=3[N:14]=[C:13]2[CH:24]=[O:25])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

Conditions

Temperature: -78 °C

Procedure

n-Butyl lithium (2.5M in hexanes, 6.8 mL, 17.1 mmol) was added to a solution of 1-phenyl-1H-imidazo[4,5-c]pyridine (1.85 g, 9.48 mmol) in THF (40 mL) at −78° C. under nitrogen. The mixture was kept at −78° C. for 15 minutes then at −10° C. for 10 minutes, and then re-cooled to −78° C. and DMF (1.5 mL, 0.190 mol) added. The reaction mixture was stirred at −78° C. for 15 minutes and −10° C. for 10 minutes. The mixture was poured into aqueous hydrochloric acid (1M, 80 mL) and the resultant mixture adjusted to pH 8 with saturated aqueous NaHCO3 (50 mL), then extracted with EtOAc (3×50 mL). The combined EtOAc extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was in purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM) to give the title compound as a yellow solid (0.72 g, 34%), containing methyl hemiacetal. LCMS (method H): Rt 1.28 min, [M+H]+ 224

Workup

waitat −10° C. for 10 minutes
extractionextracted with EtOAc (3×50 mL)
dry with materialThe combined EtOAc extracts were dried (Na2SO4)
concentrationconcentrated in vacuo
customin purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM)

Sources & evidence

ORD record: ord-4e18f1df445b4ed6b72f74592ce44708
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

Loading…