Our Capabilities

Our purpose-built PR&D labs are engineered for efficient, safe, and sustainability-led scale-up, featuring a kilo lab equipped with 20 L, 50 L and 100 L jacketed glass reactors operating across a –45 °C to 250 °C temperature range. The facilities incorporate flame-proof systems, static-discharge controls and rigorous safety engineering, supported by in-house Thermal Screening Unit (TSU) and Differential Scanning Calorimetry (DSC) capabilities to characterise and mitigate process risks early. 

We provide gram to multi-kilogram-scale delivery of intermediates, building blocks, starting materials and final compounds, supported by greener route design, solvent and reagent optimisation, and real-time analytical control. To explore our full range of equipment suite, including analytical purification systems such as SFC, Prep HPLCs and more, please refer to our official brochure here.

Our technical expertise underpinning novel, high-fidelity scale-up includes:

• Route Scouting & Process Development → Identify and optimise scalable and commercially viable synthetic pathways
• Analytical Method Development & Validation → HPLC, NMR, LCMS, etc.
• Process Safety & Scale-Up Synthesis → Safe, efficient transition to kilo-scale
• Stress Studies & Impurity Profiling → Ensure product quality and robustness
• Salt Screening & Crystallisation → Optimise solid forms and purification
• Reference Standards & COA Definition → Support for intermediates and APIs
• Indicative Stability Studies → Preliminary evaluation of intermediates and final products

Case Study: Route Development and Scale-Up of Discovery Building Block

Establishing a more reliable, scalable and sustainability-driven route for a critical chiral building block central to the multistep synthesis of a lead candidate. The initial route suffered from moderate yields, stereochemical instability at scale and a dependency on expensive or unstable reagents that compromised reproducibility and generated avoidable waste and handling risk. 
 

Challenge: A Threefold Objective

1. Establish a stereoselective route capable of delivering desired BB at kilogram scale.
2. Minimise use of sensitive reagents and achieve >99% chiral purity in final material.
3. Improve process efficiency to enable consistent supply for downstream medicinal chemistry programmes.

Solution Offered: A Structured PR&D Route-Scouting and Optimisation Strategy

• Catalyst Screening: Designed, synthesised, and evaluated several active catalysts to identify the most cost-effective and process-efficient option that provided the desired chiral purity and stability at the penultimate stage, favouring catalytic over stoichiometric approaches to minimise waste generation.
• Route Redesign with Green Chemistry Lens: Multiple literature and in-house routes were evaluated, prioritising step economy, atom efficiency, avoidance of protecting groups, and use of safer reagents and conditions before experimental validation.
• Base Optimisation: Replaced K₂CO₃ with KHCO₃ to suppress hydrolysis and racemisation during the coupling stage, significantly improving yield and product stability, while also reducing basicity-driven side reactions and downstream purification burden.
• Reagent Simplification: Eliminated the use of moisture-sensitive TMS-Br, substituting it with an HBr/AcOH system to improve yield (from 85% → 90%) and reduce handling risks and reagent costs.
• Stereoselective Refinement: Optimised a key Michael addition to deliver high enantio-control and consistent performance from grams to kilograms, ensuring scalability without resorting to extreme temperatures or conditions.
• Enhanced Quality Controls: All critical steps were validated through LCMS, chiral HPLC, and NMR monitoring, ensuring batch consistency and chiral purity, supporting real-time decision making to avoid rework and unnecessary waste.

Outcome: Reproducible process, Chiral purity >99%, overall moderate to high yield improvement.

• Scale: Delivered >13 kg of the primary BB and >10 kg of the follow-on intermediate.
• Chiral purity: >99% (final BB) and >93% (downstream intermediate).
• High-yielding steps: 91%, 90%, 62%, 85%, and 92% across key transformations.
• Route advantages: Eliminated costly reagents, shortened overall cycle time, and improved stereochemical stability, lowered waste and handling risk, making the process suitable for repeated production.

This project demonstrates our cutting-edge capabilities in delivering development-ready chemistry through the integration of green chemistry, robust process safety, and scalable process design. The optimised process established a platform for kilogram-scale BB synthesis, enabling the client’s downstream teams to carry out more than ten subsequent synthetic transformations toward their clinical lead.

For additional case studies or to learn more about our expertise, please contact us at discovery@o2h.com.