反应详情

2.95 g (11.6 mmol) of bis(2-oxo-3-oxazolidinyl)phosphinic acid chloride are added at 0° C. to a solution of 4.16 g (9.67 mmol) of (2R,4S)-2-benzyl-1-(3,5-bis-trifluoromethyl-benzoyl)-4-piperidineamine [EP 532 456 A1, Example 38 f], 1.84 g (10.6 mmol) of quinoline4-carboxylic acid and 3 ml (21.3 mmol) of triethylamine in 30 ml of methylene chloride and the ice bath is removed after 10 minutes. The reaction mixture is stirred for 4 hours at room temperature and then diluted with methylene chloride. The organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution, washed with brine, dried over magnesium sulfate and concentrated to dryness by evaporation. The crude product is chromatographed on silica gel with methylene chloride/acetone (7:3). The title compound is crystallised from methylene chloride/ether/hexane in the form of white crystals. M.p.: 187° C.; TLC: methylene chloride/acetone (7:3) Rf =0.48, FD-MS: M+ =585; [alpha]D=+9.9 (c=1, methylene chloride); analysis: calc.: C=63.59%, H=4.30%, N=7.18%, F=19.47%, found: C=63.50%, H=4.40%, N=7.16%, F=19.45%. ##STR15##

1. customthe ice bath is removed after 10 minutes
2. additiondiluted with methylene chloride
3. extractionThe organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution
4. washwashed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated to dryness by evaporation
7. customThe crude product is chromatographed on silica gel with methylene chloride/acetone (7:3)
8. customThe title compound is crystallised from methylene chloride/ether/hexane in the form of white crystals