反应详情

A solution of 1.70 g (3.65 mmol) of (2R,4S)-1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-chloro-benzyl)-piperidine4-amine and 1.5 ml (10.96 mmol) of triethylamine in 3 ml of methylene chloride is added dropwise at 0° C. to a solution of 0.915 g (4.01 mmol) of quinoline4-carboxylic acid chloride hydrochloride [Nicolai E, Gungor T, Goyard J, Cure G, Fouquet A, Teulon J M, Delchambre C, Cloarec A, Eur. J. Med. Chem., 1992, 27, 977] in 10 ml of methylene chloride. After 15 hours, a further 228 mg (1.0 mmol) of quinoline-4-carboxylic acid chloride hydrochloride and a further 0.1 ml (1.0 mmol) of triethylamine are added and the mixture is stirred for 3 hours. 1 N hydrochloric acid is added to the mixture which is then extracted with ethyl acetate. The organic phase is washed with 1 N sodium hydroxide solution and with brine, dried over sodium sulfate and concentrated. The residue is crystallised from toluene and yields the title compound in the form of white crystals. M.p. 204-207° C. (phase transition 135-140° C.); TLC: ethyl acetate: Rf =0.48, FD-MS: M+ =619(621). ##STR17##

1. extractionis then extracted with ethyl acetate
2. washThe organic phase is washed with 1 N sodium hydroxide solution and with brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated
5. customThe residue is crystallised from toluene