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Step A3: To a solution of N-(4-chloro-phenyl)-2,2-dimethyl-propionamide (product of Step A2) (14.2 mmol, 3 g) in dry THF (15 ml) under argon atmosphere, 22 ml of a 1.6 M solution of n-butyl lithium in hexanes was added at -50 C. The reaction mixture was left standing for 2 hours at 0 C. during which time a white precipitate formed. The mixture was cooled to -40 C. and solution of 2,2,2-trifluoro-1-morpholin-4-yl-ethanone (product of Step A1) (17 mmol, 3.2 g) in 10 ml of THF was added dropwise. After stirring for 1 hour at this temperature, the reaction mixture was quenched with saturated aqueous solution of ammonium chloride. The mixture was extracted with dichloromethane (2×50 ml), the organic layer was dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The crude residue was used for the next step without further purification. The residue was dissolved in dioxane and 80 ml of 3 N HCl was added. The solution was refluxed for 12 hours. After cooling to room temperature, the solution was treated with ammonia and 1 N solution of sodium hydroxide and extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, evaporated to yield a crude product. Purification was performed on silica gel via flash chromatography to obtain 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone as a yellow solid in good yield (2.6 g, 82% yield). 1H NMR (400 MHz, CDCl3): delta7.72 (m, 1H), 7.35 (m, 1H), 6.71 (d, J=9.1 Hz, 1H), 6.51 (broad s, 2H). 19F NMR (376 MHz, CDCl3): delta-69.8. 13C NMR (100 MHz, CDCl3): delta180.3 (q), 151.5, 136.9, 130.1, 130.0, 120.9, 119.0, 116.7 (q, JC-F=291.4 Hz), 111.4. |