Front Cover -- Dedication -- Practical Process Research and Development: A guide for organic chemists -- Copyright -- Contents -- About the Author -- Preface to Second Edition -- Foreword -- REFERENCES -- Chapter 1 - Introduction -- I. INTRODUCTION -- II. EQUIPMENT CONSIDERATIONS ON SCALE -- III. OPERATIONS PREFERRED ON SCALE -- IV. PATENT CONSIDERATIONS -- V. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 2 - Process Safety -- I. INTRODUCTION -- II. REPERCUSSIONS OF USING COMPOUNDS REGARDED AS ENVIRONMENTAL HAZARDS -- III. TOXICOLOGICAL HAZARDS OF COMPOUNDS -- IV. CONTROLLING CHEMICAL REACTION HAZARDS -- V. PERSPECTIVE ON SAFETY -- REFERENCES -- Chapter 3 - Route Selection -- I. INTRODUCTION -- II. GREEN CHEMISTRY CONSIDERATIONS -- III. BIOTRANSFORMATIONS -- IV. SLEUTHING TO DETERMINE ROUTES USED TO MAKE DRUGS -- V. COG ESTIMATES -- VI. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 4 - Reagent Selection -- I. INTRODUCTION -- II. BIOCATALYSIS -- III. STRONG BASES -- IV. PHASE-TRANSFER CATALYSIS -- V. PEPTIDE COUPLING -- VI. OXIDATIONS -- VII. REDUCTIONS -- VIII. TREATMENTS TO REMOVE A BOC GROUP -- REFERENCES -- Chapter 5 - Solvent Selection -- I. INTRODUCTION -- II. USING AZEOTROPES TO SELECT SOLVENTS -- III. CHOOSING SOLVENTS TO INCREASE REACTION RATES AND MINIMIZE IMPURITIES -- IV. IMPURITIES IN SOLVENTS AND REACTIONS OF SOLVENTS -- V. WATER AS SOLVENT -- VI. SOLVENT SUBSTITUTIONS -- VII. SOLVENT-FREE PROCESSES -- VIII. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 6 - Effects of Water -- I. INTRODUCTION -- II. DETECTING AND QUANTITATING WATER -- III. REMOVING WATER FROM ROUTINE ORGANIC PROCESSING -- IV. WHERE TO MONITOR AND CONTROL WATER -- V. OPERATIONS TO REMOVE OR CONSUME WATER -- VI. OPERATIONS WHERE WATER CAN BE CRUCIAL -- VII. PERSPECTIVE -- REFERENCES -- Chapter 7 - In-Process Assays, In-Process Controls, and Specifications.

I. INTRODUCTION -- II. UNDERSTANDING CRITICAL DETAILS BEHIND IN-PROCESS ASSAYS -- III. BENEFITS OF IN-PROCESS ASSAYS IN OPTIMIZING PROCESSES -- IV. IN-PROCESS CONTROLS -- V. SPECIFICATIONS -- VI. PROCESS ANALYTICAL TECHNOLOGY -- VII. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 8 - Practical Considerations for Scale-Up -- I. INTRODUCTION -- II. SAFETY: INERT ATMOSPHERES REDUCE RISKS -- III. TEMPERATURE CONTROL -- IV. HETEROGENEOUS PROCESSING AND CONSIDERATIONS FOR AGITATION -- V. ADDITIONS AND MIXING CONSIDERATIONS -- VI. SOLVENT CONSIDERATIONS -- VII. SIMPLE PROCEDURES -- VIII. IMPACT OF IPCS ON PROCESSING -- IX. CONSIDER THE VOLATILITY OF REACTION COMPONENTS, AND USE OF PRESSURE -- X. PRACTICAL CONSIDERATIONS FOR EFFICIENT WORKUPS AND ISOLATIONS -- XI. ADDITIONAL CONSIDERATIONS FOR KILO LAB OPERATIONS -- XII. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 9 - Optimizing Processes by Minimizing Impurities -- I. INTRODUCTION -- II. BENEFITS AND LIMITATIONS OF HETEROGENEOUS PROCESSING -- III. DECREASE SIDE PRODUCTS BY DECREASING DEGRADATION OF STARTING MATERIALS -- IV. CONTROLLING PH -- V. ADDITION SEQUENCE, DURATION OF ADDITION, AND TIME BETWEEN ADDITIONS -- VI. TEMPERATURE CONTROL -- VII. MINIMIZING IMPURITIES FORMED DURING WORKUP -- VIII. FACTORS AFFECTING HYDROGENATIONS -- IX. STATISTICAL DESIGN OF EXPERIMENTS -- X. REACTION KINETICS -- XI. ALTERNATIVE ADDITION PROTOCOLS, OR CONTINUOUS PROCESSING -- XII. PERSPECTIVE -- REFERENCES -- Chapter 10 - Optimizing Organometallic Reactions -- I. INTRODUCTION -- II. CHEMICAL ACTIVATION TO IMPROVE REACTION CONDITIONS -- III. OPERATIONS TO MINIMIZE SIDE REACTIONS -- IV. IMPACT OF IMPURITIES -- V. SOME CONSIDERATIONS FOR HETEROGENEOUS REACTIONS -- VI. PERSPECTIVE AND SUMMARY -- REFERENCES -- Chapter 11 - Workup -- I. INTRODUCTION -- II. QUENCHING REACTIONS -- III. EXTRACTIONS.

IV. TREATMENT WITH ACTIVATED CARBON AND OTHER ABSORBENTS -- V. FILTRATION TO REMOVE IMPURITIES -- VI. REMOVING METAL SALTS AND METALS -- VII. QUENCHING AND WORKING UP BIOCATALYTIC REACTIONS -- VIII. CHROMATOGRAPHY -- IX. PERSPECTIVE ON WORKUP -- REFERENCES -- Chapter 12 - Crystallization and Purification -- I. INTRODUCTION -- II. SLOW APPLICATION OF CRYSTALLIZATION PRESSURE, AND SEEDING -- III. CRYSTALLIZATION BY COOLING -- IV. CRYSTALLIZATION BY CONCENTRATING -- V. CRYSTALLIZATION BY ADDING AN ANTISOLVENT -- VI. REACTIVE CRYSTALLIZATION -- VII. HANDLING AND ISOLATING WATER-SOLUBLE PRODUCTS -- VIII. POLYMORPHS -- IX. PROCESSING ENANTIOMERIC CRYSTALS -- X. GUIDELINES FOR A PRACTICAL CRYSTALLIZATION -- XI. PERSPECTIVE -- REFERENCES -- Chapter 13 - Final Product Form and Impurities -- I. INTRODUCTION -- II. PHYSICOCHEMICAL CONSIDERATIONS IN APIS AND FINAL FORM SELECTION -- III. IMPURITY CONSIDERATIONS IN APIS -- IV. GENOTOXIC IMPURITIES -- V. STABILITY OF DRUG SUBSTANCE -- VI. PERSPECTIVE AND SUMMARY -- REFERENCES -- Chapter 14 - Continuous Operations -- I. INTRODUCTION -- II. MICROREACTORS AND SMALL-DIAMETER TUBING FOR SCALE-UP -- III. CONTINUOUS OPERATIONS USING TUBING OR REACTORS OF LARGER DIAMETER -- IV. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 15 - Refining the Process for Simplicity and Ruggedness -- I. INTRODUCTION -- II. THE IMPORTANCE OF MASS BALANCES -- III. DOCUMENTING A PROCESS FOR TECHNOLOGY TRANSFER -- IV. CASE STUDIES ON REFINED PROCESSES -- V. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 16 - Process Validation and Implementation -- I. INTRODUCTION -- II. LABORATORY INVESTIGATIONS FOCUSED ON PROCESS IMPLEMENTATION -- III. ACTIVITIES PRIOR TO INTRODUCING A PROCESS TO THE PILOT PLANT OR MANUFACTURING PLANT -- IV. ACTIONS DURING PROCESS IMPLEMENTATION -- V. CLEANING AND REMOVING WATER FROM PROCESSING EQUIPMENT.

VI. FOLLOW-UP AFTER PROCESS INTRODUCTION -- VII. MANAGING OUTSOURCING -- VIII. SUMMARY AND PERSPECTIVE -- REFERENCES -- Chapter 17 - Troubleshooting -- I. INTRODUCTION -- II. PERSPECTIVE -- REFERENCES -- Glossary -- General Index -- Reactions Index -- Reagents Index -- Drug Substance Index.