Asymmetric synthesis, crystal structure, and antidepressant activity of 2-aryl-3-alkyl-5-methyl-2-morpholinol hydrochlorides

2-Aryl-3-alkyl-5-methyl-2-morpholinols were synthesized from the reactions of chiral 2-aminopropan-1-ol with 2-bromo-1-phenylpropan-1-one, 2-bromo-1-(3-chlorophenyl)propan-1-one, 1-(4-(benzyloxy)phenyl)-2-bromopropan-1-one, 2-bromo-1-(6-methoxy- naphthalen-2-yl)propan-1-one, and 1-(4-(benzyloxy)phenyl)pentan-1-one in N-methyl-2-pyrrolidone (NMP), respectively. The 2-aryl-3-alkyl-5-methyl-2-morpholinols were reacted with hydrogen chloride to give the hydrochloride salts with yields of 56%-77%. The structures of the products were proven by means of their 1 H NMR, IR, and MS spectroscopic data. The stereochemical properties of representative products were established unambiguously by the X-ray single crystal analysis. The antidepressant activities of the title compounds were assayed by the mouse forced swimming test (FST). The FST results confirm the antidepressant properties of our products.Key words: morpholinol hydrochloride, hemiacetal, chiral synthesis, X-ray diffraction, absolute configuration, antidepressant activity.