Development and a Practical Synthesis of Nepafenac Intermediate via Modified Gassman Reaction

Title:Development and a Practical Synthesis of Nepafenac Intermediate via Modified Gassman Reaction

Volume: 9 Issue: 7

Author(s): Marcin Cybulski, Adam Formela, Mariola Mucha, Karolina Klos, Jacek Roszczynski and Jerzy Winiarski

Affiliation:

Keywords: Gasmann reaction, Nepafenac, N-chlorophthalimide, Sommelet-Hauser-type rearrangement, N-chloroaniline, 2-(methylthio)acetamide, chlorosulfonium, salt, sulfoxide, oxalyl

Abstract: Modification of nepafenac intermediate synthesis (5A) via Gassman specific ortho-substitution is reported. According to the process, 2-aminobenzophenone (1A) and 2-(methylthio)acetamide (2) were reacted in the convenient temperature conditions, in the presence of N-chlorophthalimide (3) or 1,3-dichloro-5,5-dimethylhydantoin (4), to activate the formation of azasulfonium salt and rearrangement thereof to pure 2-amino-3-benzoyl-α-(methylthio)phenylacetamide (5A). The procedure appears to be suitable for a reaction carried out in a large scale.

Cite this article as:

Cybulski Marcin, Formela Adam, Mucha Mariola, Klos Karolina, Roszczynski Jacek and Winiarski Jerzy, Development and a Practical Synthesis of Nepafenac Intermediate via Modified Gassman Reaction, Letters in Organic Chemistry 2012; 9 (7) . https://dx.doi.org/10.2174/157017812802139582