反应详情

910 mg (2.83 mmol) of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate and 0.8 ml (5.67 mmol) of triethylamine are added to a solution of 500 mg (1.89 mmol) of 3-(5-methyl-1H-imidazol-4-yl)propanoic acid hydrochloride in 5 ml of N,N-dimethylformamide. After 60 minutes, 1.4 g (1.89 mmol) of 2-amino-1-[-3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-3-(4-methoxyphenyl)propan-1-one trifluoroacetate dissolved in 5 ml of N,N-dimethylformamide are added. The reaction medium is stirred at room temperature for 72 hours, aqueous 1N sodium hydroxide solution is then added and the medium is extracted twice with 50 ml of a 2/8 heptane/ethyl acetate mixture. The organic phase is washed with aqueous 1N sodium hydroxide and then with aqueous 1N hydrochloric acid solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product obtained is purified by chromatography on silica gel eluted with a 90/10 dichloromethane/methanol mixture. 1 g of N-[(R)-2-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide is obtained in the form of a white solid, in a yield of 84%.

1. additionare added
2. extractionthe medium is extracted twice with 50 ml of a 2/8 heptane/ethyl acetate mixture
3. washThe organic phase is washed with aqueous 1N sodium hydroxide
4. dry with materialwith aqueous 1N hydrochloric acid solution, dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product obtained
8. customis purified by chromatography on silica gel
9. washeluted with a 90/10 dichloromethane/methanol mixture