175591-09-0

Basic information

• Product Name: Tapentadol Hydrochloride
• Synonyms: 3-[(1R,2R)-3-(Dimethylamino)-1-ethyl-2-methylpropyl]phenol Hydrochloride;Tapentadol Hydrochloride;Tapentadol hcl;Phenol, 3-[(1R,2R)-3-(diMethylaMino)-1-ethyl-2-Methylpropyl]-, (HCl salt);3-[(1R,2R)-3-(DiMethylaMino)-1-ethyl-2-Methylpro;3-((2R,3R)-1-(diMethylaMino)-2-Methylpentan-3-yl)phenol hydrochloride;Phenol,3-[(1R,2R)-3-(diMethylaMino)-1-ethyl-2-Methylpropyl]-, hydrochloride (1:1);Tapentadol hydrochloride solution
• CAS NO: 175591-09-0
• Molecular Formula: C14H24ClNO
• Molecular Weight: 257.81
• EINECS: 200-659-6
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;intermediate;Inhibitors
• Mol File: 175591-09-0.mol

Chemical Properties

• Melting Point: 178-194°C
• Boiling Point: 323.493°C at 760 mmHg
• Flash Point: 9℃
• Appearance: /
• Density: 0.97g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.518
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• CAS DataBase Reference: Tapentadol Hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Tapentadol Hydrochloride(175591-09-0)
• EPA Substance Registry System: Tapentadol Hydrochloride(175591-09-0)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 7-16-36/37-45
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 1
• Hazardous Substances Data: 175591-09-0(Hazardous Substances Data)

Usage

Chemical Properties

Light Brown Solid

Originator

Grunenthal GmbH (Germany)

Uses

A novel, centrally acting oral analgesic with a dual mode of action that has demonstrated efficacy in preclinical and clinical models of pain relief.

Brand name

Nucynta

Clinical Use

Tapentadol was approved by the FDA in November 2008 for the treatment of moderate to severe acute pain. It is a centrally acting analgesic that acts as both an agonist at the l-opiod receptor and as a norepinephrine re-uptake inhibitor, allowing it to have efficacy similar to potent narcotic analgesics but without their side effects. The drug was developed by Grunenthal and Johnson & Johnson and was marketed starting in 2009.

Side effects

The common adverse effects of tapentadol were nausea, vomiting, somnolence, dizziness, and itching. As with all opioid medications, constipation was also an issue. Tapentadol is contraindicated in patients taking monoamine oxidase inhibitors because of the potential for adverse cardiovascular events due to additive effects on norepinephrine levels. As with other MOR agonists, it is also contraindicated in patients with paralytic ileus. In patients with a history of epilepsy or seizure, tapentadol may induce seizures. Since tapentadol causes somnolence, its combination with other sleep aids could dangerously affect breathing. Similarly, patients with existing breathing or lung problems are cautioned about using tapentadol. Furthermore, patients with past or present substance abuse or drug addiction should consult the doctor prior to use since physical dependency and addiction is a risk with tapentadol. Alcohol should be avoided due to the potential additive effect on CNS depression.

Synthesis

The synthesis of tapentadol hydrochloride begins with diethyl ketone, which is subjected to a standard Mannich condition to provide a b-dimethylamino intermediate. A Grignard reaction with 3-bromoanisole was followed by the separation of diastereomers and racemic resolution. Treatment with thionyl chloride converts the hydroxy group to its corresponding chloride, which is removed by treatment with zinc borohydride (generated from zinc chloride and sodium borohydride), with overall retention of stereochemistry. The methyl ether is cleaved in refluxing HBr to afford the tapentadol salt that is ultimately converted to the hydrochloride for formulation into 50-, 75-, and 100-mg immediate-release (IR) oral tablets.

Drug interactions

Potentially hazardous interactions with other drugs Analgesics: possible opioid withdrawal with buprenorphine and pentazocine. Antidepressants: possible CNS excitation or depression with MAOIs - avoid concomitant use, and for 2 weeks after stopping MAOI; possible CNS excitation or depression with moclobemide; increased sedative effects with tricyclics. Antihistamines: increased sedative effects with sedating antihistamines. Antipsychotics: enhanced hypotensive and sedative effects. Dopaminergics: avoid with selegiline. Nalmefene: avoid concomitant use. Sodium oxybate: enhanced effect of sodium oxybate - avoid concomitant use.

Metabolism

Approximately 97% of the parent compound is metabolised by conjugation with glucuronic acid to produce glucuronides. It is also metabolised, to a lesser extent, via the cytochrome P450 isoenzymes CYP2C9, CYP2C19, and CYP2D6, before further conjugation. None of the metabolites have analgesic activity. Approximately 70% of the dose is excreted in the urine in the conjugated form and 3% as unchanged drug.

InChI:InChI=1/C14H23NO/c1-5-14(11(2)10-15(3)4)12-7-6-8-13(16)9-12/h6-9,11,14,16H,5,10H2,1-4H3/t11-,14+/m0/s1

Upstream product

• 175591-23-8 tapentadol 
• 175590-75-7 (-)-(2S,3S)-1-dimethylamino-3-(3-methoxy-phenyl)-2-methyl-pentan-3-ol hydrochloride 
• 515114-52-0 (±)-3-(1-(dimethylamino)-2-methylpentan-3-yl)phenol 
• 936116-22-2 (2S,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentane 
• 17408-16-1 3'-nitropropiophenone 
• 1309956-63-5 3-dimethylamino-2-methyl-1-(m-nitrophenyl)-1-propanone 
• 1309956-64-6 (S)-3-(dimethylamino)-2-methyl-1-(3-nitrophenyl)-propan-1-one (2R,3R)-O,O'-dibenzoyltartrate 
• 1309956-65-7 (S)-3-(dimethylamino)-2-methyl-1-(3-aminophenyl)-propan-1-one 
• 1309956-66-8 (2S,3R)-3-(3-amino-phenyl)-1-(dimethylamino)-2-methyl-pentan-3-ol 
• 1309956-67-9 C₁₈H₂₂F₆N₂O₃ 
• 1268635-18-2 (2R,3R)-dimethyl-[2-methyl-3-(3-amino-phenyl)-pentyl]-amine 
• 53013-01-7 3-(dimethylamino)-2-methyl-1-(3-nitro-phenyl)-propan-1-one 
• 2972-72-7 2-(3-methoxybenzylidene)malononitrile 
• 591-31-1 3-methoxy-benzaldehyde 

Downstream Products

• 175591-23-8 tapentadol 

Relevant articles and documents

METHOD FOR THE PREPARATION OF TAPENTADOL AND ITS INTERMEDIATES

A method for the preparation of tapentadol in the form of a base or its hydrogen chloride, which involves the preparation of a salt (III) from a mixture of diastereomers (II) by means of crystallization-induced asymmetric transformation (CIAT) through oxo

A synthetic hydrochloric acid he spurts he number of method

The invention discloses a method for synthesizing tapentadol hydrochloride. The method comprises a reaction route shown in the specification. In the reaction route, R1 is one of halogens, -OH, -OR4, -NO2, -NH2, -NR5R6, -SH and -SR7. A required chiral isomer is directly obtained through a reaction under chiral catalysis, so the method has the advantages of avoiding of problems of a large amount of wastes and environmental protection due to chiral splitting, short route, simple operation, easy industrialization, high raw material utilization rate, great improvement of the yield, cost reduction, meeting of requirements of industrial production of tapentadol hydrochloride, and significant progress.

NEW SYNTHESIS OF TAPENTADOL-HCl INTERMEDIATES

The present invention relates to a process for the synthesis of tapentadol intermediates comprising the following route of synthesis: (I) → (II) → (III) → (IV) → (V).

Novel Intermediate Used for Preparing Tapentadol or Analogues Thereof

The invention discloses a novel intermediate for preparing tapentadol and analogues thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogues thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production.

A he spurts him number of synthetic method

The invention discloses a synthetic method of tapentadol. The method comprises the following steps: reacting meta-substitution cinnamic acid serving as a starting material with a chiral adjuvant to obtain amide; reacting the amide with a nucleophilic reagent and an electrophilic reagent, and introducing two chiral centers to obtain a chiral product; performing reduction and deprotection on the chiral product to obtain chiral alcohol; performing an amination reaction and a substitution reaction on the chiral alcohol to obtain the tapentadol. The tapentadol is synthesized by taking cheap and readily-available (1R,2R)-psedo-ephedrine as the chiral adjuvant, forming two chiral centers by using a one-pot method and performing simper deprotection and subsequent transformation. By adopting the synthetic method, the reaction route can be simplified, post-treatment steps can be reduced, and the production cost is reduced. The synthetic method is more suitable for industrial application.

A NOVEL PROCESS FOR THE PREPARATION OF 1-PHENYL-3-AMINOPROPANE DERIVATIVES

The present invention relates to a novel process for the preparation of 1-phenyl-3- aminopropane derivative compounds corresponding to the formula (I) and/or its intermediates, and/or its stereo specific isomers or pharmaceutically acceptable salts, hydra

STABLE POLYMORPH FORM B OF TAPENTADOL HYDROCHLORIDE

The present invention relates to Tapentadol Hydrochloride in the polymorphic crystalline Form B, which is substantially free of polymorphic Form A as well as essentially free of low alkyl carboxylic acids or esters of such acids. Furthermore, the present

NOVEL INTERMEDIATE OF TAPENTADOL

The present invention relates to novel carbamate intermediate of formula (II), process for its preparation and process for its conversion into 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol, tapentadol and its pharmaceutically acceptable salts

Substituted n-pentanamide compounds, preparation method and the use thereof

The present invention relates to a (2R, 3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compounds as shown in the formula I and the preparation method thereof, wherein, the substituents are as defined in the specification, the present invention further relates to a use of the above compounds for the preparation of tapentadol II or its pharmaceutically acceptable salt, and the intermediates involved in the preparation process.

Compounds and Methods for Preparing Substituted 3-(1-amino-2-methylpentane-3-yl)phenyl Compounds

Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds from an isomerically pure starting material are described. In particular, methods of preparing a 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol as a substan