N-Phthaloyl-(S)-alanyl chloride as a chiral resolving agent for the kinetic resolution of heterocyclic amines

Acylative kinetic resolution of racemic amines using N-phthaloyl-(S)-amino acyl chlorides

“…Acyl chlorides 4-6 of >97% purity (according to 1 20 Freshly prepared acyl chlorides were used for further synthesis without additional purification. Acylation of 2 equiv of racemic amines 1 and 2 was carried out with 1 equiv of acyl chlorides 4-6 in a variety of solvents at various temperatures over 6 h (Scheme 3).…”

“…The same phenomena were observed previously for other amides containing the fragments of amines 1-3. [16][17][18]20 The broadening of the resonance signals is likely to be caused by the restricted rotation about a partial double amide bond and by ring inversion.…”

“…[8][9][10] Recently the methods of kinetic resolution using enantiopure chiral acylating agents have attracted considerable attention, [11][12][13][14][15] most if not all of the agents being chiral acyl-transfer agents. Our efforts have been focused on the study of kinetic resolution processes of racemic amines using low-molecular weight acylating agents, that is, chiral acyl chlorides, [16][17][18][19][20] which make it possible to obtain individual enantiomers of heterocyclic amines in good-to-high yields. It should be noted that the use of chiral acyl derivatives resulting in the formation of diastereoisomers provides an opportunity to enhance the stereochemical purity of the acylation products by traditional (non-stereospecific) methods.…”

“…20 Enantiomers of 2-methyl-1,2,3,4-tetrahydroquinoline are of interest as structural fragments of a number of biologically active compounds. [21][22][23][24] Moreover, amines 1 and 2 are close structural analogues of 7,8-difluoro-2,3-dihydro-(3S)-methyl-4H-1,4-benzoxazine (S)-3, the key intermediate in the synthesis of antibacterial Levofloxacin.…”

2-Arylpropionyl chlorides in kinetic resolution of racemic 3-methyl-2,3-dihydro-4H-[1,4]benzoxazines

“…Such an approach, which allows one to obtain individual enantiomers of chiral heterocyclic amines in high enough yields, is being successfully developed in our research group during last years. [20][21][22][23][24][25] It is known 26-29 that 2 arylpropionic acid derivatives can be used for the KR of racemic amines and alcohols. (S) Naproxen ((2S) 2 (6 methoxynaphth 2 yl)pro pionic acid) acyl chloride was for the first time used for the KR of racemic heterocyclic amines, 20,21 including 7,8 difluoro 3 methyl 2,3 dihydro 4H [1,4]benzoxazine (1) and 3 methyl 2,3 dihydro 4H [1,4]benzoxazine (2).…”