Technical Process For The Synthesis Of N-Fmoc-decyl-amino Acetaldehyde:Development And Optimization

N-Fmoc-decyl-amino acetaldehyde (PD) is the side chain of drug telavancin (TD6424). Telavancin is a new developed second generation glycopeptide antibiotic which is a semi-synthetic derivative of vancomycin. By incorporating a hydrophobic PD side chain with the vancosamine sugar, shorter median duration of therapy and better penetration into lungs has been achieved. Telavancin can beused in vancomycin intermediate sensitive strains of staphylococcus aureus (VISA) and heterogenous VISA (hVISA).The main purpose of this thesis is to develop and optimize the technical process for PD side chain synthesis.Cheap and commercially available ethanolamine and 1-bromodecane were used as the starting materials to synthesize 2-(decylamino)-ethanol, then the amino group was protected by Fmoc-Cl and the hydroxyl group was oxidized to aldehyde. The reaction conditions and work-up steps were optimized.Based on the optimized conditions obtained in laboratory, batch reactor model has been set up. Technical process for producing PD side chain in hundreds kilogram scale has been developed. Products as white solid with high yield and quality were achieved by following this process in three batchs. This result demonstrated that the optimized process was reliable for PD synthesis in factory.