98819-74-0Relevant articles and documents
The use of environmental metrics to evaluate green chemistry improvements to the synthesis of (S,S)-reboxetine succinate
Assaf, Georges,Checksfield, Graham,Critcher, Doug,Dunn, Peter J.,Field, Stuart,Harris, Laurence J.,Howard, Roger M.,Scotney, Gemma,Scott, Adam,Mathew, Suju,Walker, Geoffrey M. H.,Wilder, Alexander
, p. 123 - 129 (2012/04/11)
The Pfizer Green Chemistry metrics program is described and exemplified with a case history involving the synthesis of (S,S)-reboxetine succinate. The initial route used a classical resolution approach and generated high levels of waste. This route was replaced by an enantiospecific synthesis which used Sharpless epoxidation chemistry, an enzymatic process to selectively protect a primary alcohol and a new efficient method of chiral morpholine construction as key steps. These improvements reduced the levels of waste produced by the synthesis by more than 90%. Detailed metrics starting from a common starting material (trans-cinnamyl alcohol) for all routes of synthesis are presented.
Commercial synthesis of (S,S)-reboxetine succinate: A journey to find the cheapest commercial chemistry for manufacture
Hayes, Stewart T.,Assaf, Georges,Checksfield, Graham,Cheung, Chi,Critcher, Doug,Harris, Laurence,Howard, Roger,Mathew, Suju,Regius, Christian,Scotney, Gemma,Scott, Adam
, p. 1305 - 1314 (2012/01/14)
The development of a synthetic process for (S,S)-reboxetine succinate, a candidate for the treatment of fibromylagia, is disclosed from initial scale-up to deliver material for registrational stability testing through to commercial route evaluation and subsequent nomination. This entailed evaluation of several alternative routes to result in what would have been a commercially attractive process for launch of the compound.
Application of a process friendly morpholine synthesis to (S,S)-Reboxetine
Assaf, Georges,Cansell, Gemma,Critcher, Doug,Field, Stuart,Hayes, Stewart,Mathew, Suju,Pettman, Alan
scheme or table, p. 5048 - 5051 (2011/01/12)
We report our results on the construction of a morpholine ring system from the corresponding epoxide and amino alcohol. From this study, we were able to convert a previous four-step synthesis into a more efficient two-step process.
Process development for (S,S)-reboxetine succinate via a sharpless asymmetric epoxidation
Henegar, Kevin E.,Cebula, Mateusz
, p. 354 - 358 (2012/12/31)
Reboxetine mesylate is a selective norepinephrine uptake inhibitor (NRI) currently marketed as the racemate. The (S,S)-enantiomer of reboxetine is being evaluated for the treatment of neuropathic pain and a variety of other indications. (S,S)-Reboxetine has usually been prepared by resolution of the racemate as the (-)-mandelate salt, an inherently inefficient process. A chiral synthesis starting with a Sharpless asymmetric epoxidation of cinnamyl alcohol to yield (R,R)-phenylglycidol was developed. (R,R)-Phenylglycidol was reacted without isolation with 2-ethoxyphenol to give 4, which was isolated by direct crystallization. Key process variables for the asymmetric epoxidation were investigated. Conversion of (R,S)-4 to reboxetine parallels the racemic synthesis with streamlined and optimized processing conditions. (S,S)-Reboxetine free base was converted directly to the succinate salt without isolation as the mesylate salt.
Method for the preparation of aryl ethers
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Page 7-8, (2008/06/13)
The invention provides a method of preparing a compound of formula (I): wherein R, R1, n and m are as defined herein, or a pharmaceutically acceptable salt thereof.
