Direct One-Pot Synthesis of Propofol from Paracetamol Tablets

The COVID-19 pandemic has affected millions of people in the entire world and caused a shortage of several drugs, including propofol. Therefore, several protocols for propofol synthesis have been published in recent years. Herein, we present a process starting from paracetamol, a very common and abundant active pharmaceutical ingredient. Since the first three steps (Friedel-Crafts double alkylation, acetyl deprotection, and diazotization) are done in acidic media, a one-pot approach was developed. Furthermore, we observed that the extraction of the final product can be simplified by steam-distillation, leading to propofol in 47% isolated yield with high purity. This presented process could be an example of active pharmaceutical ingredient reuse since similar results were observed with commercial paracetamol tablets (with excipients) regardless of expiration date. © 2023 American Chemical Society.

Direct One-Pot Synthesis of Propofol from Paracetamol Tablets

The COVID-19 pandemic has affected millions of people in the entire world and caused a shortage of several drugs, including propofol. Therefore, several protocols for propofol synthesis have been published in recent years. Herein, we present a process starting from paracetamol, a very common and abundant active pharmaceutical ingredient. Since the first three steps (Friedel-Crafts double alkylation, acetyl deprotection, and diazotization) are done in acidic media, a one-pot approach was developed. Furthermore, we observed that the extraction of the final product can be simplified by steam-distillation, leading to propofol in 47% isolated yield with high purity. This presented process could be an example of active pharmaceutical ingredient reuse since similar results were observed with commercial paracetamol tablets (with excipients) regardless of expiration date. © 2023 American Chemical Society.

A Two Hour Synthesis of the Anti-Parkinson Drug Safinamide Methanesulfonate

The critical moment of the COVID-19 outbreak requires a real-time supply of therapeutic agents. Thus, time economy in the synthesis of biologically active compounds has become increasingly decisive. In this work, we developed a two hour synthesis of the anti-Parkinson drug safinamide methanesulfonate in four steps with a 64% overall yield. Microwave irradiation was used in the first three steps in a one-pot fashion. In fact, the protocol can provide safinamide free base in one hour without a chromatographic purification step. Also, green solvents such as methanol and ethyl acetate are used.