反应详情

(R)-2-(tert-butoxycarbonylamino)-2-cyclopropylacetic acid (2.25 g, 10.5 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (3.69 g, 11.5 mmol) were dissolved in dichloromethane (105 mL). 3-Cyanoazetidine hydrochloride (1.36 g, 11.5 mmol) and then N,N-diisopropylethylamine (4.5 mL, 26.1 mmol) were added and the mixture was stirred at room temperature for 5 h. Water, dilute HCl and more dichloromethane were added, the layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 2.45 g (83%) of [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.

1. customthe layers were separated
2. extractionthe aqueous layer was extracted once more with dichloromethane
3. washThe combined organic layers were washed with sodium chloride solution
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. customThe residue was purified by silica gel chromatography (methanol/dichloromethane)