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-Cl-2-Bn)-Gly-OH)

Citation
Jr. Casimir et al., 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-Cl-2-Bn)-Gly-OH), J ORG CHEM, 65(20), 2000, pp. 6487-6492
Citations number
24
Categorie Soggetti
Chemistry & Analysis","Organic Chemistry/Polymer Science
Journal title
JOURNAL OF ORGANIC CHEMISTRY
ISSN journal
00223263 → ACNP
Volume
65
Issue
20
Year of publication
2000
Pages
6487 - 6492
Database
ISI
SICI code
0022-3263(20001006)65:20<6487:ESO(>2.0.ZU;2-R
Abstract
4-Amino-2-benzazepin-3-ones have proven very useful for studying the biolog ically active conformations of peptides. The synthesis of Pht-Aba-Xaa-OH by reaction of the corresponding 1,3-oxazolidin-5-one with trifluoromethanesu lfonic 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 byp roducts 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 sy nthesis of Pht-Hba(2,6-Cl-2-Bn)-Gly-OH 17 starting from the commercially av ailable tyro sine. In our procedure, the dipeptide Pht-Tyr(2,6-Cl-2-Bn)-Gly -OH 15 is converted,to the 1,3-oxazolidin-5-one 16 Which then undergoes Fri edel-Crafts cyclization in the presence of tin tetrachloride to afford the desired 4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-2-benzaz epin-3-one 17 in excellent yield.