Reboxetine

Base Information

• Chemical Name: Reboxetine
• CAS No.: 98769-81-4
• Deprecated CAS: 98769-81-4,98769-83-6,71621-36-8
• Molecular Formula: C₁₉H₂₃NO₃
• Molecular Weight: 313.397
• UNII: 947S0YZ36I
• DSSTox Substance ID: DTXSID1048257,DTXSID401315414
• Nikkaji Number: J569.655K
• Wikipedia: Reboxetine
• Wikidata: Q72506458
• NCI Thesaurus Code: C72838
• Pharos Ligand ID: C7VKFVTWLVPU
• ChEMBL ID: CHEMBL383921
• Mol file: 98769-81-4.mol

Synonyms:2-((2-ethoxyphenoxy)benzyl)morpholine methanesulfonate;reboxetine;reboxetine mesylate;Vestra

Chemical Property of Reboxetine

Chemical Property:

• Vapor Pressure: 4.54E-08mmHg at 25°C
• Melting Point: 170-171°
• Boiling Point: 443.7°C at 760 mmHg
• Flash Point: 188.2°C
• PSA: 39.72000
• LogP: 3.52260
• XLogP3: 3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 6
• Exact Mass: 313.16779360
• Heavy Atom Count: 23
• Complexity: 333

Purity/Quality:

98%,99%, ^*data from raw suppliers

REBOXETINE 95.00% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC1=CC=CC=C1OC(C2CNCCO2)C3=CC=CC=C3
• Isomeric SMILES: CCOC1=CC=CC=C1O[C@@H]([C@H]2CNCCO2)C3=CC=CC=C3
• Recent ClinicalTrials: Efficacy of Reboxetine and Methylphenidate Treatment on Attentional, Sensory and Emotional Dysregulation in Adults With PTSD
• Recent EU Clinical Trials: The effect of various medications on emotioal processing, attention, experiences and sensory information processing
• Description: Reboxetine is a pure noradrenaline reuptake inhibitor that is licensed as an antidepressant in the United Kingdom. Reboxetine has established efficacy based on placebo-controlled studies both in the short and the long term. Previous noradrenaline reuptake inhibitors, such as desipramine, nortriptyline, and maprotiline, have been relatively selective for noradrenaline compared with serotonin but have not avoided affinities with α1, muscarinic, and histaminergic receptors. The lack of selectivity of these drugs has the consequence that the levels of cardiotoxicity are those expected with TCAs. Reboxetine is the first pure noradrenaline reuptake inhibitor, and therefore it may also provide a more appropriate agent to consider for the investigation of possible adjunctive treatments with SSRIs.
• Clinical Use: Reboxetine is a nontricyclic SNRI in which the propylamine side chain of the TCAs is constrained into a morpholine ring. It is a potent and selective ligand for the NET, with a mechanism of action is similar to that of desipramine. Reboxetine is used for the treatment of major depressive disorders. It is a chiral compound that is marketed as a racemic mixture of R,R- and S,S-reboxetine. The antidepressant activity for reboxetine appears to reside with the S,S-(+)-enantiomer, which has approximately twofold the inhibition potency of the R,R-enantiomer. It is well tolerated, with different adverse-event profiles, and it appears to be at least as effective as the SSRIs in the treatment of depressive illness. Currently, it is available only in Europe and is under U.S. FDA review. It preferentially inhibits the reuptake of NE (5-HT :NE ratio, 8). Reboxetine is not metabolized by the polymorphic isoforms, CYP2D6 or CYP2C19, and may offer a valuable alternative to the secondary amine TCAs in the treatment of major depression. Reboxetine is likely to become a promising alternative for patients who have failed treatment with or do not tolerate serotonergic antidepressants.
• Drug interactions: Reboxetine seems to be an antidepressant that has negligible interference with the pharmacokinetics of other drugs; thus, fewer drug–drug interactions are expected. It also may be possible to use reboxetine in combination with MAOIs, because it has no inhibitory effect on this enzyme, which would avoid tyramineinduced hypertensive reactions.

Technology Process of Reboxetine

There total 108 articles about Reboxetine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

(2RS,3RS)-6-<α-(2-ethoxyphenoxy)benzyl>morpholin-3-one (93886-32-9,98769-79-0,98769-80-3,98819-75-1) → reboxetine (71620-89-8,71621-36-8,93851-86-6,98769-81-4,98769-83-6,98819-76-2,105017-38-7)

Guidance literature:

With sodium bis(2-methoxyethoxy)aluminium dihydride; In toluene; for 4h; Yield given; Ambient temperature;

DOI:10.1016/S0040-4020(01)96541-X

Reference yield:

trans-2,3-epoxy-3-phenylpropan-1-ol (40641-81-4) → reboxetine (71620-89-8,71621-36-8,93851-86-6,98769-81-4,98769-83-6,98819-76-2,105017-38-7)

Guidance literature:

Multi-step reaction with 8 steps

1: 1.) NaOH / 1.) H₂O, 70 deg C; 2.) H₂O, 70 deg C, 2.5 h

2: 61 percent / pyridine / 2 h / -10 °C

3: 84 percent / Et₃N / CH₂Cl₂ / 0.5 h / 0 - 5 °C

4: 2N NaOH / dioxane / 4 h / Ambient temperature

5: 32percent NH₄OH / methanol / 6 h / sealed flask

6: 98 percent / Et₃N / CH₂Cl₂ / 0.5 h / -10 - -5 °C

7: 86 percent / t-BuOK / 2-methyl-propan-2-ol / 3 h / Ambient temperature

8: RED-AL / toluene / 4 h / Ambient temperature

With ammonium hydroxide; sodium hydroxide; potassium tert-butylate; triethylamine; sodium bis(2-methoxyethoxy)aluminium dihydride; In 1,4-dioxane; pyridine; methanol; dichloromethane; toluene; tert-butyl alcohol;

DOI:10.1016/S0040-4020(01)96541-X

Reference yield:

(2RS,3RS)-3-(2-ethoxyphenoxy)-3-phenylpropene-1,2-epoxide (98769-72-3,98819-72-8) → reboxetine (71620-89-8,71621-36-8,93851-86-6,98769-81-4,98769-83-6,98819-76-2,105017-38-7)

Guidance literature:

Multi-step reaction with 4 steps

1: 32percent NH₄OH / methanol / 6 h / sealed flask

2: 98 percent / Et₃N / CH₂Cl₂ / 0.5 h / -10 - -5 °C

3: 86 percent / t-BuOK / 2-methyl-propan-2-ol / 3 h / Ambient temperature

4: RED-AL / toluene / 4 h / Ambient temperature

With ammonium hydroxide; potassium tert-butylate; triethylamine; sodium bis(2-methoxyethoxy)aluminium dihydride; In methanol; dichloromethane; toluene; tert-butyl alcohol;

DOI:10.1016/S0040-4020(01)96541-X

upstream raw materials:

(2RS,3RS)-6-<α-(2-ethoxyphenoxy)benzyl>morpholin-3-one

2-Ethoxyphenol

benzaldehyde

trans-2,3-epoxy-3-phenylpropan-1-ol

Downstream raw materials:

(S,S)-reboxetine

(2R,3R)-reboxetine

(S,S)-reboxetine (S)-mandelate

(2S,3S)-2-[α-(2-ethoxyphenoxy)benzyl]morpholine succinate

Refernces

• 1、 -. "Sulfoxide ligand metal catalyzed oxidation of olefins". Page/Page column 171. . Retrieved 2019/05/09.
• 2、 Liu, Cheng,Lin, Zhi-Wei,Zhou, Zhao-Hui,Chen, Hong-Bin. "Stereodivergent synthesis of all the four stereoisomers of antidepressant reboxetine". . p. 5395 - 5401. Retrieved 2017/07/10.