2-Bromopropane → 6-Chloro-4-(3-chloro-phenyl)-2-isopropoxy-quinoline-3-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

To the stirred solution of 6-chloro-4-(3-chloro-phenyl)-2-hydroxy-quinoline-3-carboxylic acid tert-butyl ester (prepared as described in example 91 step B, 400 mg, 1.02 mmol) in 8 ml DMF was added NaH (60%, 65 mg, 1.54 mmol) portion wise at 0° C. and the resulting reaction mixture was stirred for 30 min at 25° C. Then the reaction mixture was cooled to 0° C. and a solution of 2-bromo-propane (0.192 ml, 2.05 mmol) was added dropwise in 2 ml DMF. The reaction mixture was stirred for 16 h at 50° C. and then quenched with saturated aqueous ammonium chloride solution (10 ml). Subsequently the mixture was diluted with water (25 ml) and extracted with ethyl acetate (3×60 ml). The organic phases were combined and was washed with brine (25 ml), dried over sodium sulfate and concentrated in vacuo to give a crude residue which was purified by column chromatography eluting with 2% ethyl acetate in hexane to yield 6-chloro-4-(3-chloro-phenyl)-2-isopropoxy-quinoline-3-carboxylic acid tert-butyl ester (290 mg, 65% yield) as an off white solid. LC-MS (ESI): 432 (M+H)+.

Provenance & Evidence