Preparation of Benzyl(( R )‐2‐(4‐(benzyloxy)phenyl)‐2‐(( tert ‐Butoxycarbonyl)Amino)Acetyl)‐D‐Phenylalaninate Using Umpolung Amide Synthesis

Abstract

A procedure yielding Benzyl ((R)‐2‐(4‐(benzyloxy)phenyl)‐2‐((tert‐butoxycarbonyl)amino)acetyl)‐D‐phenylalaninate as a beige solid is presented. Notes on the paraphernalia and chemicals to be used during each procedures are provided. The chapter concludes with a brief discussion on arylglycine α‐amino amides.

A Metal-Free Three-Component Reaction of trans-β-Nitrostyrene Derivatives, Dibromo Amides, and Amines Leading to Functionalized Amidines

“…An intensive solvent screening was undertaken (Table , entries 6–11, and Table S1, entries 19–27), showing that the use of dichloromethane and dichloroethane give the best results. Thus, previous reported solvents for peptide bond formation, , such as DME/H 2 O, THF/H 2 O, and acetonitrile, gave lower yields. Oxygen, which was reported to assist the synthesis of peptide bond, , did not promote the peptide bond formation but on the other hand had no negative effect, simplifying the reaction procedure (Table , entry 12).…”

“…Thus, previous reported solvents for peptide bond formation, , such as DME/H 2 O, THF/H 2 O, and acetonitrile, gave lower yields. Oxygen, which was reported to assist the synthesis of peptide bond, , did not promote the peptide bond formation but on the other hand had no negative effect, simplifying the reaction procedure (Table , entry 12).…”

“…Aliphatic nitro compounds are versatile building blocks that provide unique opportunities for the construction of multifunctionalized carbon frameworks. − Recently, presynthesized α-bromo-substituted nitroalkanes were disclosed as atypical precursors for N-acylating species by Johnston and co-workers. They can be oxidized with N -iodosuccinimide (NIS) and molecular oxygen in the presence of amines to form a peptide bond . Furthermore, Hayashi and co-workers demonstrated that primary nitroalkanes and α,α-dihalonitroalkanes could be used as alternative reagents for the amide synthesis .…”