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Tert-Butyl Bromoacetate: Applications in the Synthesis of MRI Contrast Agents and Green Preparation

Oct 31，2024

Description

tert-Butyl bromoacetate binds to amines and β-amino acids with high affinity and has been shown to have a binding constant of 10M for the human serum albumin. It also binds to nitrogen atoms, which can be seen in its nmr spectra, and is used in asymmetric synthesis due to its carbonyl group. Tert-butyl bromoacetate is used in site specific reactions because of its amide group, which can be cleaved by hydrolysis or by reductive conditions.

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Applications in the Synthesis of MRI Contrast Agents

DOTA is an octadentate ligand with four carboxylate and four amino groups which coordinate with lanthanide ions. Consequently, their complexes with DOTA possess high thermodynamic stability and kinetic inertness, making these compounds useful in MRI as contrast agents.

C-functionalized DOTA-type ligands can be prepared by intramolecular or intermolecular cyclization methods using appropriate scaffolds. For instance, the intramolecular cyclization of tosyl amide (prepared from tetrapeptide followed by borane reduction and tosylation) at high dilution and subsequent detosylation with a concentrated strong acid results in C-functionalized cyclen. Its alkylation with tert-butyl bromoacetate, followed by hydrolysis yields a C-functionalized DOTA-type ligand 1. This synthesis has been improved by initiating the cyclization of diamine with carbamate-protected disuccinimido ester at high-dilution at a higher temperature (90 °C). Using these synthetic approaches, a number of different C-functionalized DOTA can be prepared by a simple variation of side arm (R′).

Green Preparation

The green preparation method for tert-butyl bromoacetate is a sustainable and efficient process that prioritizes environmental friendliness. the synthetic method of a bromo-acetic acid tert-butyl, it is characterized in that: bromoacetic acid and tert.-butyl acetate are by weight mixing for 4:1 ~ 1:1, bromoacetic acid is all dissolved in tert.-butyl acetate, enter again a reactor that strong acid ion exchange resin is housed, control temperature 30-45 ℃, through the reaction of 2 ~ 6 hours, generate containing bromo-acetic acid tert-butyl weight content 20-45% mixture, by two rectifying tower separation, obtain more than 99% bromo-acetic acid tert-butyl of purity again.

Reference

1. Nevenka Cakić, Serhat Gündüz, Rathikrishnan Rengarasu, Goran Angelovski,Synthetic strategies for preparation of cyclen-based MRI contrast agents,Tetrahedron Letters,Volume 56, Issue 6,2015,Pages 759-765.

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