methyl 5,5,5-trifluoro-3-oxopentanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to example 10 step B from 4-chloro-2-(2-chloro-phenylethynyl)-phenylamine (prepared as described in example 10 step A, 300 mg, 1.14 mmol), 5,5,5-trifluoro-3-oxo-pentanoic acid methyl ester (prepared as described in example 34 step A, 421.4 mg, 2.29 mmol) and p-TsOH.H2O (326.54 mg, 1.72 mmol). Yellow solid (90 mg, 18% yield). LC-MS: 442 (M+H)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-amino-5-chloro-phenyl)-phenyl-methanone (120 mg, 0.52 mmol) and 5,5,5-trifluoro-3-oxo-pentanoic acid methyl ester (124 mg, 0.67 mmol) in 5 ml ethanol at room temperature was added ytterbium triflate (32 mg, 0.05 mmol). The reaction mixture was stirred for 16 h at room temperature, upon which a white precipitate was formed. The precipitated solid was filtered and washed with ethanol to afford 6-chloro-4-phenyl-2-(2,2,2-trifluoro-ethyl)-quinoline-3-carboxylic acid methyl ester (70 mg, 36%) as an off white solid. LC-MS: 380 (M+H)+. was formed The precipitated solid was filtered washed with ethanol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2,2-dimethyl-[1,3]dioxane-4,6-dione (200 mg, 1.41 mmol), pyridine (0.125 ml, 1.55 mmol) and DMAP (344 mg, 2.81 mmol) in dichloromethane (10 ml), was added 3,3,3-trifluoro-propionyl chloride (0.16 ml, 1.55 mmol) at 0° C. The resulting reaction mixture was stirred under nitrogen for 1 h at 0° C. and then allowed to warm to room temperature and stirred for 2 h. Volatiles were removed under reduced pressure, and the crude residue was diluted with diethyl ether and washed with 1 N HCl. The organic layer was dried and concentrated to get the intermediate, which was diluted with 10 ml of methanol and refluxed for 5 h. Volatiles were removed under reduced pressure to afford the crude 5,5,5-trifluoro-3-oxo-pentanoic acid methyl ester (120 mg, 46%) as brown liquid which was used in the following step without further purification. FIA-MS: 183 (M−H)−. The resulting reaction mixture to warm to room temperature stirred for 2 h Volatiles were removed under reduced pressure the crude residue was diluted with diethyl ether washed with 1 N HCl The organic layer was dried concentrated to get the intermediate, which refluxed for 5 h Volatiles were removed under reduced pressure