Diisopropylamine → trans-1-Methyl-3-diethylamino-4-phenyl-2-azetidinone

Participants

Reaction Steps

13.33 ml of 1.5 molar n-butyllithium in hexane, equivalent to 20 mmoles n-butyllithium, was added to a solution of 2.02 g (20 mmoles) of diisopropylamine in 25 ml benzene. The resulting solution of lithium diisopropylamide was stirred for 10 min. Then 3.18 g (20 mmoles) of the corresponding enantiomerically pure N,N-diethylglycine menthyl ester was added causing an exothermic reaction. The resulting solution was stirred for 30 min. Then a solution of 2.73 g (20 mmoles) of zinc dichloride in 20 ml of diethyl ether was added resulting in a yellow solution. This solution was stirred for 10 min. Most of the diethyl ether and hexane present in solution was evaporated in vacuo. 2.38 g (20 mmoles) of N-(benzylidene)methylamine was added to the resulting benzene solution and the reaction mixture refluxed for 70 min. During this period some solid material precipitated. The reaction mixture was cooled down to room temperature and diluted with 20 ml of diethyl ether. 15 ml of a saturated aqueous ammonium chloride solution was added to the reaction mixture. The organic phase was separated and was washed twice with 15 ml portions of a saturated aqueous ammonium chloride solution and twice with 15 ml portions of water. The organic phase was extracted with 2 portions of 20 ml 4 molar HCl solution in water. The acidic aqueous phase was washed 3 times with 20 ml portions of diethyl ether. The aqueous phase was made basic with a concentrated ammonia solution and extracted with three 20 ml portions of diethyl ether. The organic extract was dried with sodium sulfate and concentrated in vacuo yielding 3.5 g (75%) of the 2-azetidinone as a white solid, with the same properties as those given for example IIA.

Provenance & Evidence