Hydrochloric Acid → HCID 178471175, compound

Participants

Reaction Conditions

Reaction Steps

A solution comprising ethyl 2-(4,5,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)propionate dihydrochloride (60.2 g, 0.20 mol) in acetonitrile (400 mL) was cooled to 0° C. under nitrogen, treated with N,N-diisopropylethylamine (35 mL, 0.20 mol), further cooled to ˜−5° C. (ice/acetone) and then treated with benzyl chloroformate (58 mL, 0.41 mol) and N,N-diisopropylethylamine (70 mL, 0.40 mol) in alternating portions over 30 minutes. The mixture was cooled at −5° C. for 1 hour and allowed to warm to 20° C. and, after 16 hours, concentrated under reduced pressure. The residue was suspended in ether and the suspension was washed successively with sodium bicarbonate, sodium chloride, 0.1M hydrochloric acid and sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was dissolved in ethanol (320 mL) and the solution was cooled to −5° C. under nitrogen and then sodium ethoxide (21 wt %, 85 mL, 0.22 mol) was added dropwise over 1 hour while the reaction temperature was maintained below 0° C. The mixture was cooled at −5° C. for 1 hour, adjusted to neutral pH with 50 mL of 4M hydrochloric acid and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the solution was washed with sodium bicarbonate and sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexanes/ethyl acetate) to provide benzyl 2-(1-ethoxycarbonylethyl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate (52 g, 72%) as a pale yellow oil; 1H-NMR (300 MHz, DMSO-d6) d ppm: 11.72 (br s, 1H), 7.32 (s, 5H), 5.07 (s, 2H), 4.32 (br s, 2H), 4.02 (q, 2H, J=9.3 Hz), 3.77 (q, 1H, J=8.3 Hz), 3.66 (s, 2H), 2.55 (s, 2H), 1.38 (d, 3H, J=8.3 Hz), 1.13 (t, 3H, J=9.3 Hz).

Provenance & Evidence