200801-70-3

Basic information

• Product Name: rac 5-Hydroxymethyl Tolterodine, 90% by HPLC
• Synonyms: rac 5-Hydroxymethyl Tolterodine, 90% by HPLC;BenzeneMethanol, 3-[3-[bis(1-Methylethyl)aMino]-1-phenylpropyl]-4-hydroxy-;3-[3-[Bis(1-Methylethyl)aMino]-1-phenylpropyl]-4-hydroxybenzeneMethanol;2-(3-(diisopropylaMino)-1-phenylpropyl)-4-(hydroxyMethyl)phenol;Fesoterodine IMpurity A;Tolterodine 5-HydroxyMethyl Analog RaceMate;racemic 5-hydroxymethyl tolterodine;rac 5-Hydroxymethyl Tolterodine
• CAS NO: 200801-70-3
• Molecular Formula: C₂₂H₃₁NO₂
• Molecular Weight: 341.48704
• Product Categories: Various Metabolites and Impurities;Inhibitors;Intermediates & Fine Chemicals;Metabolites;Pharmaceuticals;Metabolites & Impurities
• Mol File: 200801-70-3.mol

Chemical Properties

• Melting Point: 52-53°C
• Boiling Point: 490.721°C at 760 mmHg
• Flash Point: 233.165°C
• Appearance: /
• Density: 1.061g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.563
• Storage Temp.: -20°C Freezer
• Solubility: Acetonitrile (Slightly), Chloroform (Slightly)
• PKA: 9.61±0.48(Predicted)
• CAS DataBase Reference: rac 5-Hydroxymethyl Tolterodine, 90% by HPLC(CAS DataBase Reference)
• NIST Chemistry Reference: rac 5-Hydroxymethyl Tolterodine, 90% by HPLC(200801-70-3)
• EPA Substance Registry System: rac 5-Hydroxymethyl Tolterodine, 90% by HPLC(200801-70-3)

Safety Data

• Hazardous Substances Data: 200801-70-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C22H31NO2/c1-16(2)23(17(3)4)13-12-20(19-8-6-5-7-9-19)21-14-18(15-24)10-11-22(21)25/h5-11,14,16-17,20,24-25H,12-13,15H2,1-4H3

Upstream product

• 959624-24-9 (2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl)methanol 
• 108-18-9 diisopropylamine 
• 250214-39-2 (-)-N,N-diisopropyl-3-(2-benzyloxy-5-hydroxymethylphenyl)-3-phenylpropylamine 
• 214601-16-8 N,N-diisopropyl-3-(2-hydroxy-5-methyloxycarbonylphenyl)-3-phenylpropanamine 
• 2687-12-9 cinnamyl chloride 
• 87462-12-2 N,N-diisopropyl-3-phenyl-2-propen-1-amine 
• 21087-29-6 trans-3-phenylprop-2-enyl chloride 
• 173948-30-6 (E)-N,N-diisopropyl-3-phenylprop-2-en-1-amine 
• 156755-23-6 6-bromo-4-phenyl-3,4-dihydro-2H-chromen-2-one 
• 250214-37-0 (+/-)-toluene-4-sulphonic acid 3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl ester 
• 1349883-68-6 (+/-)-4-bromo-2-(3-hydroxy-1-phenylpropyl)phenol 
• 14371-10-9 (E)-3-phenylpropenal 
• 623-05-2 (4-hydroxyphenyl)methanol 
• 126070-20-0 4-((tert-butyldimethylsilyloxy)methyl)phenol 

Downstream Products

• 207679-81-0 (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)-phenol 
• 286930-02-7 fesoterodine 
• 156755-20-3 PNU 200577 l-mandelate salt 
• 286930-03-8 fesoterodine fumarate 
• 1350462-15-5 lithium (R)-(+)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenol 
• 286930-03-8 fesoterodine fumarate 
• 260389-90-0 5-hydroxymethyl tolterodine 
• 1333234-72-2 (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol (R)-2-acetoxy(phenyl)acetate 

Relevant articles and documents

Photochemistry of a novel antimuscarinic drug fesoterodine and identification of its photodegradation products by LC-ESI-MS studies

Fesoterodine (FESO) is a novel muscarinic receptor antagonist for the treatment of overactive bladder syndrome. The aim of this work was to study the photodegradation of FESO, to determine its kinetics and to identify the photodegradation products. The photochemistry of FESO was investigated in sample solutions exposed to a UV-A (320-400 nm) and UV-C irradiation (100-280 nm) at room temperature. The photodegradation process was monitored by means of liquid chromatography method equipped with monolithic column and photodiode array detector. This drug is more photolabile under UV-C light. In methanol-water solution (1:1, v/v), approximately 62.5% of FESO decomposes after 60 min of UV-C irradiation, whereas under 6 h of UV-A light only 4.9% decomposes. FESO was shown to be photolabile and its photodegradation reaction followed the zero-order kinetics with the rate constant k = 0.5503 min-1, and t1/2 and t90% obtained were 46.92 min and 9.38 min, respectively. The main degradation products were isolated by semi-preparative liquid chromatography and identified by liquid chromatography coupled to an electrospray ionization mass spectrometry. The powdered and intact tablets were also exposed to UV-C irradiation. Based on the obtained results, a complete drug photodegradation pathway was proposed.

Synthetic Method of Intermediate for Fesoterodine

The present invention relates to a method for producing 3-(3-diisopropylamino-1-phenylpropyl)-4-hydroxy benzenemethanol, which is an intermediate product useful for producing fesoterodine, by using ethyl benzoylacetate as a starting material. The producin

Formal synthesis of fesoterodine by acid-facilitated aromatic alkylation

The competitive muscarinic receptor antagonist fesoterodine is a congener of tolterodine and has better efficiency compared to tolterodine. In this study, we present an efficient synthesis of the fesoterodine intermediate 3-(3-diisopropylamino-1-phenylpropyl)-4-hydroxybenzaldehyde from ethyl benzoylacetate by Friedel-Crafts alkylation in the presence of an acid as a key reaction step. The synthesis is carried out by the reduction of the ketoester to a 1,3-diol, diisopropylamine substitution, and Friedel-Crafts alkylation, followed by reduction and chiral resolution.

PROCESS FOR THE PREPARATION OF 2-HYDROXY-4-PHENYL-3,4-DIHYDRO-2H-CHROMEN-6-YL-METHANOL AND (R)-FESO-DEACYL

The present invention regards an improved and industrially advantageous process for the preparation of the 2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called “feso chromenyl” and (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol, also called “(R)-feso deacyl”, which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine fumarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate “(R)-feso deacyl”, called form B.

The lactol route to fesoterodine: An amine-promoted Friedel-Crafts alkylation on commercial scale

We report the discovery and optimization of an amine-promoted Friedel-Crafts alkylation of cinnamaldehyde with 4-hydroxymethyl phenol. This reaction has been used successfully on commercial scale (200 kg) in the context of the manufacture of fesoterodine, a muscarinic antagonist used for the treatment of overactive bladder. Reductive aminations of diisopropylamine and lactol 4 are also discussed, as well as the resolution of the racemic amine rac-2 into its enantiomerically pure form.

PREPARATION PROCESS OF FESOTERODINE AND INTERMEDIATES

The present invention relates to a process of synthesis of 3,3 dipheylpropylamines, which may be used as pharmaceutical intermediates in the preparation of their pharmacologically active derivatives such as fesoterodine, tolterodine, their enantiomers, pharmaceutically acceptable salts and related compounds useful as antimuscarinic agents.

PROCESS FOR THE PREPARATION OF 2 -HYDROXY- 4 -PHENYL -3, 4 -DIHYDRO-2H-CHROMEN- 6 -YL -METHANOL AND (R) - FESO - DEACYL

The present invention regards an improved and industrially advantageous process for the preparation of the 2-hyaroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called "feso chromenyl" and (R)-2-[3-(diisopropylamino)-l- phenylpropyl]-4-(hydroxymethyl)phenol, also called "(R)-feso deacyl", which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine furnarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate "(R)-feso deacyl", called form B.

PROCESS FOR PREPARATION OF PHENOLIC MONOESTERS OF HYDROXYMETHYL PHENOLS

Disclosed herein is an improved and efficient process for preparation of fesoterodine and its pharmaceutically acceptable salt. Disclosed also herein is novel intermediate of formula (III). Also disclosed are metal salts of formula (XII) and preparation thereof.

PROCESS FOR PREPARATION OF PHENOLIC MONOESTERS OF HYDROXYMETHYL PHENOLS

A process for the preparation of phenolic monoesters of 2-(3-diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)phenol by converting (±)6-halo-4-phenylchroman-2-one to (±)4-halo-2-(3-hydroxy-1-phenylpropyl)phenol. The two hydroxyl groups are protected and the protected compound is reacted with diisopropylamine to give (±)[3-(2-benzyloxy-5-halophenyl)-3-phenylpropyl]diisopropylamine. The halo substituent on the benzene ring is converted to corresponding benzyl alcohol and then the protection is removed to give racemic 5-HMT. Racemic 5-HMT is converted R enantiomer and then it is esterified.

SHORT SYNTHESIS OF TOLTERODINE, INTERMEDIATES AND METABOLITES

A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)- 1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.