Sodium Carbonate → Ethyl 5-([2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-5-fluorophenyl)ethyl]{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate

Participants

Reaction Steps

685 mg (2.36 mmol) of methyl 4-(2-iodoethyl)benzoate and 188 mg (1.77 mmol) of anhydrous sodium carbonate were added to a solution of 740 mg (1.18 mmol) of ethyl 5-{[2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}-5-fluorophenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate dihydrochloride (Enantiomer 2, Example 116A) in 20 ml of dry acetonitrile, and the mixture was heated under reflux overnight. A further 342 mg of methyl 4-(2-iodoethyl)benzoate were then added, and the mixture was stirred under reflux overnight. This procedure was repeated two more times on the subsequent days. Then, another 342 mg of methyl 4-(2-iodoethyl)benzoate and 188 mg of anhydrous sodium carbonate were added and the mixture was again stirred under reflux overnight. Another 342 mg of methyl 4-(2-iodoethyl)benzoate were then added to the reaction solution, and the mixture was heated under reflux overnight and then cooled to room temperature. The reaction was filtered, the filter cake was washed with acetonitrile and the filtrate was concentrated to dryness. The residue was taken up in ethyl acetate, and water was added. The organic phase was separated, dried over magnesium sulphate, filtered and evaporated to dryness. The residue obtained was purified chromatographically on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1→4:1). This gave 588 mg (0.40 mmol, 63% of theory) of the title compound.

Provenance & Evidence