403-29-2

456-00-8

The general procedure for the synthesis of α-amino-p-fluoroacetophenone hydrochloride from 2-bromo-4'-fluoroacetophenone was as follows: Intermediate 5A was prepared by the method described in PCT Publication No. WO 2009/137081 (PCT US2009/002845), which was carried out as follows: To a solution of chloroform (65.5 mL) containing 2-bromo-1-(4-fluorophenyl)ethanone (6.57 g, 30.3 mmol) Hexamethylenetetramine (4.37 g, 30.8 mmol) was added to a solution of chloroform (65.5 mL) containing 2-bromo-1-(4-fluorophenyl)ethanone (6.57 g, 30.3 mmol). The reaction mixture was stirred at room temperature for 16 hours and then filtered to collect a white solid. The solid was suspended in methanol (130 mL) followed by the slow addition of concentrated hydrochloric acid (~8.6 mL). The resulting homogeneous reaction mixture was refluxed for 4 hours. Upon completion of the reaction, the mixture was cooled, filtered to remove the inorganic salt, and the filter cake was washed with methanol (~30 mL). The filtrates were combined and concentrated under reduced pressure to give a solid product, which was then dried under high vacuum for 2 hours. Further purification by silica gel column chromatography (using a Thomson BIOTAGE column eluting with a gradient of 5% to 20% dichloromethane solution in methanol) gave a red solid product. The solid was dissolved in a small amount of dichloromethane and filtered to give Intermediate 5A as a colorless solid (5.44 g, 95% yield).HPLC retention time: 0.90 min (Method D). Mass spectrum (electrospray ionization): m/z = 136.05 [M + H]+.