Sandoz Ag

Alphora Research Inc.

Robert Jordan

Boris Gorin

Fabio E S Souza

Craig Edward Dixon

Ming Pan

Dino Alberico

Alena Rudolph

Fabio Es Souza

Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R, R, R, R, R, R, R, R, R, R, R, R, Rand Rare as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed. 

[object Object]

Disclosed is a continuous process for the preparation of ingenol-3-mebutate by reaction, in solution, of ingenol or ingenol anion and angelic anhydride or an equivalent angelylating agent. The continuous flow process is preferably performed in the presence of a base such as lithium hexamethyl disilazane (LiHMDS) and/or an activating agent such as dicyclohexylcarbodiimide (DCC). Also disclosed is a process for recycling the other reaction products obtained in the continuous process for preparation of ingenol-3-mebutate for formation of ingenol, which can then be recycled to form ingenol-3-mebutate. 

Continuous flow process for the preparation of Ingenol-3-mebutate

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Rockwood, Canada

Robert Jordan