Bromination of codeine and its derivatives: Revisiting a 95 year old process

A safe and practical methodology was developed for the bromination of codeine and its derivatives using NBA (N-bromoacetamide) in the presence of TFAA (trifluoroacetic anhydride). The described protocol provides a viable alternative to the commonly used approach developed about a century ago, which requires hydrogen bromide gas as a reagent. In contrast, this facile and safe bromination occurs under mild conditions, has a broad scope, and provides the desired products in good to excellent yields. (C) 2020 Elsevier Ltd. All rights reserved.