The general procedure for the synthesis of 5-fluoroisoindolin-1-one from methyl 2-cyano-4-fluorobenzoate was as follows: a solution of Raney nickel (4.00 g) and methyl 2-cyano-4-fluorobenzoate (2.00 g, 11.2 mmol) in ethanol (20 mL) under nitrogen protection was added to a 250 mL Parr reactor. The reactor was connected to a Parr hydrogenation unit, evacuated and filled with hydrogen to a pressure of 50 psi and reacted under shaking conditions for 16 hours. Upon completion of the reaction, the hydrogen was withdrawn and refilled with nitrogen. Diatomaceous earth 521 (5.00 g) was added to the reaction mixture and filtered through a diatomaceous earth 521 pad. The filter cake was washed with ethanol (2 x 75 mL), the filtrates were combined and concentrated to dryness under reduced pressure to afford the colorless oily product 5-fluoroisoindolin-1-one in 76% yield (1.29 g). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3): δ 7.85 (dd, 1H, J = 8.5, 5.5 Hz), 7.21-7.16 (m, 2H), 7.05 (br s, 1H), 4.56 (s, 2H).
