1,4-Dioxane hydrochloride → (2S)-2-Amino-N,N-dimethyl-3-phenylpropanamide hydrochloride

Participants

Reaction Steps

To the compound (I) (19.00 g), 4 N hydrogen chloride/1,4-dioxane solution (325 ml) was added under room temperature, and the mixture was stirred at the same temperature for 30 minutes. The mixture was concentrated under a reduced pressure, and L-phenylalanine dimethylamide hydrochloride (II) was obtained quantitatively as a white powder. Subsequently, to a solution of the compound (II), trans-4-(t-butoxycarbonylaminomethyl)cyclohexylcarboxylic acid (16.70 g) and triethylamine (9.75 ml) in dry dichloromethane (200 ml), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (13.69 g) was added under ice-cooling, the mixture was stirred for 2 hours, and again stirred at room temperature for 2 hours. To the reaction water was added to obtain an organic layer, which was washed with 10% aqueous citric acid, water, 5% aqueous sodium hydrogen carbonate, and water, in this order, followed by drying over anhydrous sodium sulfate. The solids were filtered off, the filtrate concentrated under a reduced pressure and the residue was washed with diethyl ether, followed by filtration to give N-[trans-4-(t-butoxycarbonylaminomethyl)cyclohexylcarbonyl]-L-phenylalanine dimethylamide (III) (21.90 g). The structure was confirmed by NMR.

Provenance & Evidence