[Synthesis]
Step 1: Diphenyl phosphate azide (DPPA, 27.5 g, 0.1 mol) was added dropwise to a solution of (E)-3-(4-chlorophenyl)acrylic acid (18.3 g, 0.1 mol) and triethylamine (Et3N, 20.2 g, 0.2 mol) in benzene (100 mL). After stirring the reaction mixture for 2 h, the solution was concentrated and purified by fast chromatography (Biotage system, mobile phase 20/80 ethyl acetate/hexane) to give 16 g of the intermediate azide as a solid. The intermediate was dissolved in 100 mL of 1,2-dichloroethane and the resulting mixture was slowly heated to 90 °C over 30 min. The reaction mixture was then heated to reflux and held at this temperature for 3 hours. After cooling to room temperature, a solid was precipitated, collected by filtration and washed with toluene to give 9.5 g of 7-chloroisoquinolin-1(2H)-one in 53% yield.
Product characterization data.
1H NMR (400 MHz, CD3OD) δ ppm: 6.66 (d, J = 7.05 Hz, 1H), 7.18 (d, J = 7.05 Hz, 1H), 7.66 (s, 1H), 7.67 (d, J = 2.01 Hz, 1H), 8.24 (d, J = 2.27 Hz, 1H).
13C NMR (101 MHz, DMSO-D6) δ ppm: 104.05, 125.62, 127.21, 128.54, 129.52, 130.77, 132.43, 136.55, 160.72.
LC/MS, MS m/z (M + H)+: 180. |