ToolFusion Chemical
ToolFusion Chemical
📋 Case Study

Pharmaceutical API Synthesis Redesign at Novartis Basel

High E-factor (>100), hazardous chlorinated solvents, 30% yield loss in final crystallization

🏗️ Project Overview

Redesign of multi-step synthesis for antihypertensive drug candidate

🎯 Challenge

High E-factor (>100), hazardous chlorinated solvents, 30% yield loss in final crystallization

🔧 Design Approach

Switched to bio-based ethyl acetate, introduced catalytic asymmetric hydrogenation, integrated continuous crystallization with inline PAT

📐 Design Diagram

Pharmaceutical API Synthesis Redesign Novartis Basel | E-Factor ↓78% | Solvent Intensity: 2.1 → 0.4 kg/kg CHALLENGES • E-Factor >100 • Chlorinated solvents • 30% yield loss (crystallization) DESIGN APPROACH • Bio-based EtOAc • Catalytic asymmetric hydrogenation • Continuous crystallization + inline PAT RESULTS E-Factor ↓ 78% Solvent Intensity 2.1 → 0.4 kg/kg API Δ E-Factor >100 ✓ EtOAc ↑ PAT Process Mass Intensity (PMI) driven improvement | Continuous flow + green chemistry

AI-generated project design illustration

📐 Key Calculations

E-Factor Reduction

(Old PMI − New PMI) / Old PMI × 100
Result: 78%
Direct waste reduction metric

Solvent Intensity Drop

kg solvent/kg API
Result: 2.1 → 0.4
Toxicity and recovery cost driver

📊 Results

E-factor reduced from 112 to 24; solvent-related incidents eliminated; annual waste disposal cost cut by $1.2M

💡 Lessons Learned

  • •Catalyst selection must balance activity, leaching risk, and end-of-life recovery
  • •PAT integration enables real-time sustainability KPI tracking

✅ Key Takeaways

  • 1Catalyst selection must balance activity, leaching risk, and end-of-life recovery
  • 2PAT integration enables real-time sustainability KPI tracking