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

Participants

Reaction Conditions

Reaction Steps

A suspension of 69 g (111.24 mmol) of ethyl 5-{[2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 86A), 129 g (444.98 mmol) of methyl 4-(2-iodoethyl)benzoate and 17.68 g (166.87 mmol) of anhydrous sodium carbonate in 1500 ml of dry acetonitrile was stirred at a bath temperature of 110° C. overnight. A further 65.54 g of methyl 4-(2-iodoethyl)benzoate and 23.06 g (166.87 mmol) of powdered potassium carbonate were then added, and the mixture was heated under reflux for another 48 h. After cooling of the reaction mixture, the inorganic salts were filtered off and the filtrate obtained was evaporated to dryness. The resulting residue was taken up in ethyl acetate, washed twice with 10% strength aqueous sodium chloride solution, dried over magnesium sulphate, filtered and then once more evaporated to dryness. The residue obtained was purified chromatographically on silica gel (3 kg) (mobile phase: petroleum ether/ethyl acetate 8:2→7:3). This gave 42 g (54.45 mmol, 49% of theory) of the target compound.

Provenance & Evidence