635724-55-9

Basic information

• Product Name: Esreboxetine succinate
• Synonyms: (2S)-2-[(S)-(2-ETHOXYPHENOXY)PHENYLMETHYL]MORPHOLINE SUCCINATE;Esreboxetine succinate
• CAS NO: 635724-55-9
• Molecular Formula: C19H23NO3.C4H6O4
• Molecular Weight: 431.48
• Mol File: 635724-55-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: 149-152 °C
• Appearance: /
• CAS DataBase Reference: Esreboxetine succinate(CAS DataBase Reference)
• NIST Chemistry Reference: Esreboxetine succinate(635724-55-9)
• EPA Substance Registry System: Esreboxetine succinate(635724-55-9)

Safety Data

• Hazardous Substances Data: 635724-55-9(Hazardous Substances Data)

Usage

General Description

Esreboxetine succinate is a pharmaceutical compound that acts as a selective norepinephrine reuptake inhibitor. It is used as a treatment for major depressive disorder and neuropathic pain. Esreboxetine succinate works by blocking the reuptake of norepinephrine, a neurotransmitter that plays a role in regulating mood and pain perception. By increasing the levels of norepinephrine in the brain, esreboxetine succinate is able to alleviate depressive symptoms and reduce neuropathic pain. This chemical has shown promising results in clinical trials and is considered a valuable option in the treatment of these conditions.

InChI:InChI=1/C19H23NO3.C4H6O4/c1-2-21-16-10-6-7-11-17(16)23-19(15-8-4-3-5-9-15)18-14-20-12-13-22-18;5-3(6)1-2-4(7)8/h3-11,18-20H,2,12-14H2,1H3;1-2H2,(H,5,6)(H,7,8)/t18-,19-;/m0./s1

Upstream product

• 110-15-6 succinic acid 
• 71620-89-8 (S,S)-reboxetine 
• 104968-70-9 (S,S)-reboxetine (S)-mandelate 
• 1250978-71-2 2-{[(2S,3S)-3-(2-ethoxyphenoxy)-2-hydroxy-3-phenylpropyl]amino}ethyl hydrogen sulfate 
• 1333116-46-3 (S)-4-benzoyl-2-[(R)-hydroxyphenylmethyl]morpholine 
• 1333116-37-2 (4-benzoylmorpholin-2-yl)phenylmethanone 
• 98819-74-0 N-[(2S,3S)-3-(2-ethoxyphenoxy)-2-hydroxy-3-phenylpropyl]-2-chloroacetamide 
• 1340546-27-1 (2S,3S)-3-(2-ethoxyphenoxy)-2-hydroxy-3-phenylpropylamine benzoate 
• 1340546-28-2 C₁₉H₂₂O₅ 
• 1356958-70-7 C₂₀H₂₄O₇S 
• 93853-04-4 (2RS,3RS)-1-amino-3-(2-ethoxyphenoxy)-2-hydroxy-3-phenylpropane methanesulfonate 
• 98819-77-3 (+)-(2S,3S)-2-<α-(2-ethoxyphenoxy)benzyl>morpholine methanesulfonate 
• 98769-72-3 (-)-(2S,3S)-3-(2-ethoxyphenoxy)-3-phenylpropene-1,2-epoxide 
• 93851-63-9 (2RS,3RS)-1-amino-3-(2-ethoxyphenoxy)-2-hydroxy-3-phenylpropane 

Relevant articles and documents

The use of environmental metrics to evaluate green chemistry improvements to the synthesis of (S,S)-reboxetine succinate

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

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.

Process development for (S,S)-reboxetine succinate via a sharpless asymmetric epoxidation

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.