Maxacalcitol Synthesis with Available Materials for Mass Production
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Solution Overview
Problem
Existing processes for preparing maxacalcitol are not suitable for mass production due to the difficulty in supplying starting materials and the complexity of multiple steps and conditions.
Innovation Solution
A process involving ozonolysis, Baeyer-Villiger oxidation, Horner-Wadsworth-Emmons reaction, hydrolysis, nucleophilic substitution, and deprotection of intermediates to efficiently produce maxacalcitol, using compounds of specific formulas as starting materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If the existing process using DHEA as starting material is used, then maxacalcitol can be prepared, but it is very difficult to supply starting materials and not suitable for mass production
Solution Approach 1:
The patent changes the starting material from DHEA (formula 2) to a commercially available compound (formula 1) and modifies reaction parameters including using a different solvent system (dichloromethane/methanol mixture), adjusting temperature ranges, and changing reaction time to achieve both ease of manufacture and mass production capability
Solution Approach 2:
The patent employs readily available, inexpensive starting materials and common reagents (ozone, dimethyl sulfide, sodium borohydride, etc.) that can be easily sourced and disposed of, making the process suitable for large-scale production rather than requiring specialized or expensive materials
2Manufacturing precision
If the existing process with multiple steps is used, then maxacalcitol can be prepared, but it is not suitable for mass production due to multiple steps and certain conditions
Solution Approach 1:
The patent combines multiple reaction steps into a more streamlined sequence: ozonolysis and reduction are performed together in one pot, followed by Baeyer-Villiger oxidation, then Horner-Wadsworth-Emmons reaction. This merging reduces the number of isolation and purification steps while maintaining product quality
Solution Approach 2:
The patent segments the synthesis into distinct modular stages (ozonolysis/reduction, Baeyer-Villiger oxidation, HWE reaction, deprotection) that can be independently optimized and controlled, allowing for better quality management while reducing overall process complexity compared to the prior art
3Reliability
If the existing process is used, then maxacalcitol can be prepared, but it is not cost-effective for mass production
Solution Approach 1:
The patent uses inexpensive, commercially available starting materials and common reagents throughout the synthesis pathway, eliminating the need for expensive or specialized chemicals. This dramatically reduces material costs while maintaining product efficacy through carefully controlled reaction conditions
Solution Approach 2:
The patent optimizes reaction parameters including temperature, solvent ratios, and reaction times to maximize yield and minimize waste. The use of readily available reagents and simplified workup procedures reduces both material and processing costs, making the process cost-effective for mass production
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The process allows for the efficient and cost-effective production of maxacalcitol intermediates and the final compound, suitable for large-scale manufacturing.
Implementation Method 1
subjecting a compound of the following formula (2) to ozonolysis and reduction to obtain a compound of the following formula (3)
Implementation Method 2
subjecting a compound of the following formula (2) to ozonolysis and reduction to obtain a compound of the following formula (3)
Implementation Method 3
subjecting the compound of the following formula (3) to Baeyer-Villiger oxidation to obtain a compound of the following formula (4)
Implementation Method 4
subjecting the compound of the following formula (4) to Homer-Wadsworth-Emmons reaction with a compound of the following formula (6)
Implementation Method 5
subjecting a formate group of a compound of the following formula (5) to hydrolysis to obtain a compound of the following formula (7)
Data Source
AI summary
A new and improved method for preparing maxacalcitol and an intermediate therefor is provided. The method is an efficient and cost-effective process for preparing maxacalcitol and an intermediate therefor.