Toluene → ethyl 2-[3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]-3-furoate

Participants

Reaction Conditions

Reaction Steps

N-(2-chloroethyl)acetamide (1.21 g) in ethyl acetate (10 mL) was added over 10 min to a stirred suspension of phosphorus pentachloride (2.08 g) in ethyl acetate (2 mL) at 0° C. under nitrogen to give a clear pale straw solution. After 45 min at 0° C. toluene (12 mL) was added, and ethyl 2-(3-aminophenyl)-3-furoate hydrochloride (1.78 g) was added in one portion into the above solution at 0–5° C. The mixture was stirred at 0–5° C. for 10 min and then allowed to warm up to 20° C. After 2 h formation of the amidine is essentially complete (HPLC ethyl 2-(3-aminophenyl)-3-furoate hydrochloride <2% @ 220 nm, a/a). The mixture was cooled to 0–5° C., crushed ice (18 g) was added over 20 min to destroy phosphorus oxychloride. Ammonium hydroxide (28%, 6.49 mL) was added at a rate that the internal temperature was kept below 25° C. (ca. 15 min). After 1 h at 20° C. additional ethyl acetate (12 mL) added to the above mixture, the organic layer was separated, washed with deionized water (2×12 mL), and concentrated under reduced pressure. The residue was dissolved in acetone (5 mL) and ethyl acetate (5 mL), and treated with oxalic acid (0.72 g) at 40° C. for 30 min. After aging at <20° C. for at least 12 h, the precipitate was collected by filtration, washed with acetone (2×0.5 vol), and dried in vacuo at 45–50° C. to yield 1.9 g (73%) of white solid. 1H NMR (400, d6-DMSO) δ: 8.00 (s, 1H), 7.92–7.90 (m, 2H), 7.64–7.55 (m, 2H), 6.90 (d, 1H), 4.32 (t, 2H), 4.22 (q, 2H), 3.93 (t, 2H), 2.22 (s, 3H), 1.24 (t, 3H).

Provenance & Evidence