Hydrochloric Acid → HCID 178469170, compound

Participants

Reaction Steps

A solution of 1-methylpyrrolidin-2-one (14.81 ml, 154 mmol) in anhydrous 1,2-dichloroethane (DCE) (250 ml) under a nitrogen atmosphere was added drop wise POCl3 (28.5 ml, 307 mmol) over a 10 min period and the mixture was stirred at ambient temperature. After 1 h, a solution of diethyl 2-(1-aminoethylidene)malonate (30.9 g, 154 mmol) in DCE (10 mL) was added and the mixture was heated to 40° C. After 18 h, the reaction mixture was partitioned between sat. aq. NaHCO3 and DCM. The organic later was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo, The residue was dissolved in N,N-dimethylformamide (DMF) (150 ml) and treated dropwise with sodium ethoxide (172 ml, 461 mmol) and heated to 100° C. After 3 h, the reaction mixture was cooled to ambient temperature and the pH was adjusted to pH 7 with 1M HCl. The mixture was partitioned between water and EtOAc and the organics washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified on silica gel (EtOAc-hexanes, 0-25%) to afford ethyl 4-hydroxy-1,6-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (11.0 g, 30.3% yield) as a white solid. 1H NMR (CHLOROFORM-d) δ: 11.89 (s, 1H), 4.37 (q, J=7.0 Hz, 2H), 3.54 (t, J=8.7 Hz, 2H), 2.87-3.05 (m, 5H), 2.64 (s, 3H), 1.41 (t, J=7.1 Hz, 3H); LC/MS (m/z) ES+=237.1 (M+1)+

Provenance & Evidence