Abstract
The synthesis of Etidronate (as the disodium salt) by the reaction of acetic acid with phosphorus trichloride/ phosphorus acid in methanesulfonic acid was studied and optimized. We showed that it is enough to use 3.2 equivalents of the phosphorus trichloride and there is no need to apply phosphorus acid. In the two-step variation of the synthesis, the acetyl chloride was formed by the reaction of acetic acid with phosphorus trichloride, thionyl chloride or triphosgene, then the intermediate was converted to etidronate by reaction with 2.2 equivalents of phosphorus trichloride. The work-up included in all cases hydrolysis and pH adjustment.
Keywords: Hydroxy-methylenebisphosphonic acid, Etidronate, Optimization, Intermediate.
Letters in Drug Design & Discovery
Title:Optimized Synthesis of Etidronate
Volume: 10 Issue: 8
Author(s): Rita Kovacs, David Illes Nagy, Alajos Grün, Gyorgy Tibor Balogh, Sandor Garadnay, Istvan Greiner and Gyorgy Keglevich
Affiliation:
Keywords: Hydroxy-methylenebisphosphonic acid, Etidronate, Optimization, Intermediate.
Abstract: The synthesis of Etidronate (as the disodium salt) by the reaction of acetic acid with phosphorus trichloride/ phosphorus acid in methanesulfonic acid was studied and optimized. We showed that it is enough to use 3.2 equivalents of the phosphorus trichloride and there is no need to apply phosphorus acid. In the two-step variation of the synthesis, the acetyl chloride was formed by the reaction of acetic acid with phosphorus trichloride, thionyl chloride or triphosgene, then the intermediate was converted to etidronate by reaction with 2.2 equivalents of phosphorus trichloride. The work-up included in all cases hydrolysis and pH adjustment.
Export Options
About this article
Cite this article as:
Kovacs Rita, Nagy Illes David, Grün Alajos, Balogh Tibor Gyorgy, Garadnay Sandor, Greiner Istvan and Keglevich Gyorgy, Optimized Synthesis of Etidronate, Letters in Drug Design & Discovery 2013; 10 (8) . https://dx.doi.org/10.2174/15701808113109990026
DOI https://dx.doi.org/10.2174/15701808113109990026 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Heparin-Binding Proteins (Chemokines and Defensins) and their Complexes with Glycosaminoglycans from the Solution NMR Perspective
Current Protein & Peptide Science Neurobiological Mechanisms of Stress Resilience and Implications for the Aged Population
Current Neuropharmacology Plasticity and Maintenance of Hematopoietic Stem Cells During Development
Recent Patents on Biotechnology NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Current Medicinal Chemistry Global Cell Proteome Profiling, Phospho-signaling and Quantitative Proteomics for Identification of New Biomarkers in Acute Myeloid Leukemia Patients
Current Pharmaceutical Biotechnology Nature and Nurture in the Early-Life Origins of Metabolic Syndrome
Current Pharmaceutical Biotechnology Ginger for Prevention or Treatment of Drug-Induced Nausea and Vomiting
Current Clinical Pharmacology Dietary Small Molecules and Large-Scale Gene Expression Studies: An Experimental Approach for Understanding their Beneficial Effects on the Development of Malignant and Non-Malignant Proliferative Diseases
Current Medicinal Chemistry Investigation of Nanoemulsion System for Transdermal Delivery of Domperidone: Ex-vivo and in vivo Studies
Current Nanoscience Topical Calcineurin Inhibitors, Pimecrolimus and Tacrolimus
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Evolution of Schizophrenia: A Model for Selection by Infection, with a Focus on NAD
Current Pharmaceutical Design Microglial Integrity is Maintained by Erythropoietin Through Integration of Akt and Its Substrates of lycogen Synthase Kinase-3β, β-Catenin, and Nuclear Factor-κB
Current Neurovascular Research Cellular Functions of RNA-Binding Motif Protein 3 (RBM3): Clues in Hypothermia, Cancer Biology and Apoptosis
Protein & Peptide Letters Cefepime and its Role in Pediatric Infections
Recent Patents on Anti-Infective Drug Discovery Cytotoxic and Antitumoral Activity of N-(9H-purin-6-yl) Benzamide Derivatives and Related Water-soluble Prodrugs
Current Molecular Pharmacology Phosphonomethoxyalkyl Analogs of Nucleotides
Current Pharmaceutical Design Pharmacological Approaches to Chronic Spinal Cord Injury
Current Pharmaceutical Design Familial Hypercholesterolemia: Update and Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Cancer Stem Cells and the Tumor Microenvironment: Soloists or Choral Singers
Current Pharmaceutical Biotechnology Herbal Formulation Against Dental Caries Causing Microorganisms Using Extracts of Stevia Rebaudiana Leaves (A Natural Sweetner)
The Natural Products Journal