Efficient synthesis of (S)-4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)- 3-oxo-2H-2-benzazepin-2-acetic acid (PHt-Hba(2,6-Cl2-Bn)-Gly-OH).
4-Amino-2-benzazepin-3-ones have proven very useful for studying the biologically active conformations of peptides. The synthesis of Pht-Aba-Xaa-OH by reaction of the corresponding 1,3-oxazolidin-5-one with trifluoromethanesulfonic acid (TFMSA) has been reported in the literature. However, when this procedure was applied to the preparation of Pht-Hba(Bn)-Gly-OH 8, many byproducts were formed and the yield of the desired aminobenzazepinones 7 and 8 was very low. We report in this paper an efficient methodology for the synthesis of Pht-Hba(2,6-Cl2-Bn)-Gly-OH 17 starting from the commercially available tyrosine. In our procedure, the dipeptide Pht-Tyr(2,6-Cl2-Bn)-Gly-OH 15 is converted to the 1,3-oxazolidin-5-one 16 which then undergoes Friedel-Crafts cyclization in the presence of tin tetrachloride to afford the desired 4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-2-be nzazepin-3-one 17 in excellent yield.
Casimir
J R
JR
Vrije Universiteit Brussel, Department of Organic Chemistry, Belgium. R.Casimir@ibmc.u-strasbg.fr
Tourwé
D
D
Iterbeke
K
K
Guichard
G
G
Briand
J P
JP
D001552:Benzazepines / Q000138:chemical synthesis*; D004151:Dipeptides / Q000737:chemistry; D007202:Indicators and Reagents; D008968:Molecular Conformation; D010797:Phthalimides / Q000138:chemical synthesis*
C416064:4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-3-oxo-2H-2-benzazepin-2-acetic acid; D001552:Benzazepines; D004151:Dipeptides; D007202:Indicators and Reagents; D010797:Phthalimides