Stereo- and regioselective synthesis of chiral diamines and triamines from pseudoephedrine and ephedrine

Synthesis and characterization of new 2-(alkylamino)acetamides

“…As confirmed by 1 H NMR the reaction of bromoacetamide 1 and β-aminoalcohols 2f, 2h and 2j leads to 2-(aminoalkyl)acetamides 3f, 3h and 3j which are transformed into the corresponding morpholin-2-ones 5,12 in aproximatly 30%, after 12 hours under reflux except for 3j. Moreover, 2-(aminoalkyl)acetamides 3f, 3h, 3i and 3j were allowed to stand for one month in chloroform solution which resulted in 40% conversion to the morpholine-2-ones, except for 3j (Scheme 2).…”

“…They have also been used as precursors in the synthesis of vicinal diamides, morpholin-2-ones, 5 and as ligands in the synthesis of organometallic compounds with potential anti-tumor activity. 6 2-(Alkylamino)acetamides have been prepared by reaction of 2-chloro-N,N-dimethylacetamide or 2-(alkylamino)methylacetate with amines and β-aminoalcohols, in the presence of sodium bicarbonate or triethylamine.…”

“…6 2-(Alkylamino)acetamides have been prepared by reaction of 2-chloro-N,N-dimethylacetamide or 2-(alkylamino)methylacetate with amines and β-aminoalcohols, in the presence of sodium bicarbonate or triethylamine. 5,[7][8] It is noteworthy that the reaction of 2-chloro-N,Ndimethylacetamide with ephedrines, in the presence of sodium bicarbonate, under reflux of benzene for 20 hours provides both 2-(alkylamino)acetamides and morpholin-2-ones, while the use of triethylamine as base yields exclusively the corresponding 2-(alkylamino)-acetamides. In contrast, when this reaction is carried out under reflux of xylene, the morpholin-2-one is formed exclusively.…”

“…In contrast, when this reaction is carried out under reflux of xylene, the morpholin-2-one is formed exclusively. 5 Our current interest in 2-(alkylamino)acetamides prompted us to develop better reaction condition to synthesize these compounds in good yields. Thus, we describe herein the synthesis and characterization of seven new 2-(alkylamino)acetamides 3a-j (Scheme 1).…”

Efficient diastereoselective synthesis of (1R,2R)-1-alkyl-1-phenyl-2-methylaminopropanes and study of stereochemical aspects

“…Thus, chlorination of (1S,2R)-1-alkyl-1-phenyl-2-methylaminopropan-1-ol hydrochloride 11a-g at C-1 is expected to undergo via S N 2 mechanism resulting in inversion of configuration at the reaction center to obtain corresponding (1R,2R)-1-alkyl-1-chloro-1-phenyl-2-methylaminopropane hydrochloride 13a-g ( Table 2). The possible formation of aziridinium ion [15][16][17] by intramolecular rearrangement of amino chloride is inhibited as the chlorination is performed with the quaternary salt of the 1,2-aminoalcohol where the lone pair on nitrogen is not available for the cyclization to yield an aziridinium ion. Further, catalytic hydrodehalogenation of the chloro intermediates brings about another inversion, 18 leading to overall retention of configuration at C-1 (Scheme 4).…”