Reaction Steps
To a solution of 3-methoxyphenyl hydrazine (2.01 g, 11.53 mmol) and 6-fluoro-1-indanone (1.73 g, 11.50 mmol) in ethanol (22 mL) was added glacial acetic acid (3 drops). The solution was stirred at reflux (85° C.) for 15 minutes and cooled to room temperature. Ethanol was removed in vacuo and the resulting brown oil was dissolved in isopropanol (39 mL). Sulfuric acid (36N, 1.28 mL) was added via syringe and the solution was stirred at reflux (90° C.) for 15 hours and subsequently cooled to room temperature. The reaction was then basified to pH 10 via addition of aqueous sodium hydroxide (2% by mass) resulting in the formation of precipitate. The solid was collected by vacuum filtration to yield a brown residue, which was subsequently dissolved in 20 mL dichloromethane, and diluted with 15 mL H2O. The organic layer was partitioned and the aqueous layer was extracted 1×15 mL ethyl acetate and 1×15 mL dichloromethane. Organic layers were pooled, dried over anhydrous magnesium sulfate, and concentrated to yield 55 as a mixture of regioisomers (3:1 55:undesired). Crude product was brought on to the next step without further purification. 1H NMR (600 MHz, CDCl3): δ 8.17 (s, 1H), 7.50 (d, J=8.4 Hz), 7.38-7.41 (dd, 1H, J=8.4, 5.4 Hz), 7.05-7.07 (dd, 1H, J 9.0, 2.4 Hz), 6.927 (d, 1H, J=2.4 Hz), 6.83-6.86 (m, 2H), 3.87 (s, 3H), 3.63 (s, 2H). 13C NMR (150 MHz, CDCl3): δ 162.4 (d, J=241.5 Hz), 156.6, 142.4 (d, J=2.4 Hz), 141.7, 141.3 (d, J=3.0 Hz), 136.8 (d, J=9.6 Hz), 125.8 (d, J=9.2 Hz), 124.0, 119.7, 119.1, 110.3 (d, J=22.7 Hz), 110.0, 104.2 (d, J=24.5 Hz), 96.1, 60.4, 29.8. 19F NMR (CD3CD, 376 MHz): δ −113.9 (m), −115.9 (m); FTIR: cm−1 3381, 1614, 1531, 1464, 1270, 1188, 1157, 859, 814. ESI-HRMS: Calcd. for C16H12FNO+ [M]+: 253.0897, found 253.0894.
