209747-04-6

Basic information

• Product Name: Tolterodine Lactol IMpurity
• Synonyms: Tolterodine Lactol IMpurity;rac-6-Methyl-4-phenyl-2-chroManol (Tolterodine IMpurity);6-methyl-4-phenyl-3,4-dihydro-2H-chromen-2-ol;Tolterodine Impurity 13
• CAS NO: 209747-04-6
• Molecular Formula: C₁₆H₁₆O₂
• Molecular Weight: 240.29704
• Mol File: 209747-04-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 80-81 °C
• Boiling Point: 377.2±42.0 °C(Predicted)
• Appearance: /
• Density: 1.173±0.06 g/cm3(Predicted)
• PKA: 12.71±0.40(Predicted)
• CAS DataBase Reference: Tolterodine Lactol IMpurity(CAS DataBase Reference)
• NIST Chemistry Reference: Tolterodine Lactol IMpurity(209747-04-6)
• EPA Substance Registry System: Tolterodine Lactol IMpurity(209747-04-6)

Safety Data

• Hazardous Substances Data: 209747-04-6(Hazardous Substances Data)

Usage

Description

Tolterodine Lactol IMpurity, also known as rac-6-Methyl-4-phenyl-2-chromanol, is an impurity found in Tolterodine (T535800), which is an antimuscarinic agent used to treat patients with overactive bladder. It is a chemical compound that may be present during the synthesis or manufacturing process of Tolterodine and is important to monitor and control for quality and safety reasons.

Uses

Used in Pharmaceutical Industry:
Tolterodine Lactol IMpurity is used as a quality control parameter for the production of Tolterodine, an antimuscarinic agent. It is essential to monitor and control the levels of this impurity to ensure the safety and efficacy of the final drug product used in the treatment of overactive bladder.
Tolterodine Lactol IMpurity is used as a reference material for the development and validation of analytical methods in the pharmaceutical industry. This helps in the accurate identification and quantification of the impurity, which is crucial for maintaining the quality and consistency of Tolterodine products.
Tolterodine Lactol IMpurity is also used as a research tool in the study of the synthesis, stability, and degradation pathways of Tolterodine. Understanding the behavior of this impurity can contribute to the optimization of manufacturing processes and the development of new, more effective treatments for overactive bladder.

Upstream product

• 959624-36-3 1,4-bis-(6-methyl-4-phenyl-chroman-2-yl)-piperazine 
• 14371-10-9 (E)-3-phenylpropenal 
• 106-44-5 p-cresol 
• 40546-94-9 6-methyl-4-phenyl-3,4-dihydrocoumarin 
• 108-18-9 diisopropylamine 
• 201230-82-2 carbon monoxide 
• 62594-94-9 1-[(2-hydroxy-5-methyl)phenyl]-1-phenylethylene 
• 536-74-3 phenylacetylene 
• 140-10-3 (E)-3-phenylacrylic acid 

Downstream Products

• 124936-74-9 N,N-diiso-propyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine 
• 518360-75-3 4-methyl-2-(1-phenyl-3-pyrrolidine-1-ylpropyl)phenol 

Relevant articles and documents

Hydrolase-mediated resolution of the hemiacetal in 2-chromanols: The impact of remote substitution

Hydrolase-catalysed dynamic kinetic resolutions of chroman-2-ol and 3-methyl chroman-2-ol can be effected with up to 88% conversion and 92% ee through the use of organic solvents. Extension to the resolution of the tolterodine precursor 1 proved more challenging. The presence of the remote phenyl substituent had a significant impact on the resolution and it was not possible to achieve high enantioselectivity together with efficient conversion from the focussed panel of enzymes screened.

ENANTIOSELECTIVE SYNTHESIS OF ENANTIOMERICALLY ENRICHED COMPOUNDS

Method of preparing an enantiomerically enriched compound of formula (II) comprising enantioselective hydrogenation of a compound of general formula (I): where W, X and Z have the meanings indicated in the description, to give a compound of general formula (II): where W, Y, T and C* have the meanings indicated in the description, in the presence of a catalyst or its suitable precursor based on Rh, Ru or Ir, having an oxidation state of 0, +1 or +2, and containing at least one enantiomerically enriched chiral ligand.

A new efficient route to Tolterodine

Tolterodine, an important urological drug, can be conveniently prepared starting from 1-[2-hydroxy-5-methyl)phenyl]-1-phenylethylene, accessible in high yield by alumina-promoted ortho alkenylation of p-cresol with phenylacetylene. The hydroformylation of this olefin, catalyzed by rhodium complexes both in homogeneous or in aqueous biphasic system, affords the desired linear aldehyde in about 80-90% yield. The reductive amination of this aldehyde, in the presence of HN-(iPr)2 and Pd/C (5%) as the catalytic precursor at 4 atm H2 and 48°C, produces directly tolterodine in more than 90% yield. Some experiments of enantioselective hydroformylation of 1-[2-hydroxy-5-methyl)phenyl]-1-phenylethylene catalyzed by Rh(CO)2acac/(S,R)-Binaphos and other enantiopure ferrocenyldiphosphines afforded only low yields of the expected chiral aldehyde; unfortunately, the achieved ee did not exceed 8%.