Efficient continuous flow synthesis of ethyl shikimate: the first step in the synthesis of Tamiflu

Ethyl shikimate is the first intermediate in the synthesis of oseltamivir phosphate (Tamiflu). Commercially, it is synthesised from the esterification of (-)-shikimic acid with ethanol in the presence of SOCl2 in batch. Herein is a comprehensive study on the continuous flow synthesis of ethyl shikimate in >90% yield and less than 10min residence time. Furthermore due to environmental, health and safety concerns over the use of SOCl2, the use of safer and more environmentally friendly reagents was investigated. Numerous effective continuous flow synthetic procedures for ethyl shikimate have been developed successfully.