57415-36-8

Basic information

• Product Name: N-(2-pyridylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide
• Synonyms: EINECS 260-729-7;N-(2-Pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide;N-(2-Pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (Flecainide Impurity);N-(2-Pyridinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (Flecainide;Flecainide IMpurity E;Flecainide acetate impurity E (EP)
• CAS NO: 57415-36-8
• Molecular Formula: C₁₇H₁₄F₆N₂O₃
• Molecular Weight: 408.30
• EINECS: 260-729-7
• Product Categories: Aromatics;Heterocycles;Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 57415-36-8.mol
• Article Data: 6

Chemical Properties

• Melting Point: 99-101°C
• Boiling Point: 441.1 °C at 760 mmHg
• Flash Point: 220.6 °C
• Appearance: /
• Density: 1.372 g/cm³
• Vapor Pressure: 5.6E-08mmHg at 25°C
• Refractive Index: 1.489
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• CAS DataBase Reference: N-(2-pyridylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2-pyridylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide(57415-36-8)
• EPA Substance Registry System: N-(2-pyridylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide(57415-36-8)

Safety Data

• Hazardous Substances Data: 57415-36-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 57415-36-8 differently. You can refer to the following data:
1. Flecainide impurity. A novel intermediate for the preparation of Flecainide.
2. Flecainide

InChI:InChI=1/C17H14F6N2O3/c18-16(19,20)9-27-12-4-5-14(28-10-17(21,22)23)13(7-12)15(26)25-8-11-3-1-2-6-24-11/h1-7H,8-10H2,(H,25,26)

Synthetic route

(2-aminomethylpyridine) (3731-51-9) + 2,5-bis(2,2,2-trifluoroethoxy)-α,α-dibromo-α-chloroacetophenone (389082-83-1) → 2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide (57415-36-8)

Conditions	Yield
In hexane; toluene	93.4%

(2-aminomethylpyridine) (3731-51-9) + 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid chloride (50778-59-1) → 2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide (57415-36-8)

Conditions	Yield
With triethylamine In water; benzene

(2-aminomethylpyridine) (3731-51-9) + C14H12F6O6 → 2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide (57415-36-8)

Conditions	Yield
In ethyl acetate at 15 - 25℃; for 1h;

(2-aminomethylpyridine) (3731-51-9) + 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid (35480-52-5) → 2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide (57415-36-8)

Conditions	Yield
Stage #1: 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid With pivaloyl chloride; triethylamine In dichloromethane; N,N-dimethyl acetamide at -30 - -20℃; Stage #2: 2-(Aminomethyl)pyridine In dichloromethane; N,N-dimethyl acetamide at -20℃; for 2h; Stage #3: With sodium carbonate In dichloromethane; N,N-dimethyl acetamide; water Product distribution / selectivity;
Stage #1: 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid With chloroformic acid ethyl ester; triethylamine In dichloromethane; N,N-dimethyl acetamide at -30 - -20℃; Stage #2: 2-(Aminomethyl)pyridine In dichloromethane; N,N-dimethyl acetamide at -20℃; for 2h; Stage #3: With sodium carbonate In dichloromethane; N,N-dimethyl acetamide; water Product distribution / selectivity;
Stage #1: 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid With pivaloyl chloride; triethylamine In dichloromethane; N,N-dimethyl-formamide at -30 - -20℃; Stage #2: 2-(Aminomethyl)pyridine In dichloromethane; N,N-dimethyl acetamide at -20℃; for 2h; Stage #3: With sodium carbonate In dichloromethane; water; N,N-dimethyl-formamide Product distribution / selectivity;
Stage #1: 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid With 4-methyl-morpholine; pivaloyl chloride In dichloromethane; N,N-dimethyl acetamide at -30 - -20℃; Stage #2: 2-(Aminomethyl)pyridine In dichloromethane; N,N-dimethyl acetamide at -20℃; for 2h; Stage #3: With sodium carbonate In dichloromethane; N,N-dimethyl acetamide; water Product distribution / selectivity;

2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide (57415-36-8) → flecainide acetate (54143-56-5)

Conditions	Yield
Pt-C In acetic acid	89%

2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide (57415-36-8) + acetic acid (64-19-7) → flecainide acetate (54143-56-5)

Conditions	Yield
Stage #1: 2,5-bis(2,2,2-trifluoroethoxy)-N-(pyridin-2-ylmethyl)-benzamide With hydrogen; acetic acid; palladium 10% on activated carbon; platinum on carbon at 69 - 72℃; under 2925.29 - 4425.44 Torr; for 5h; Stage #2: With sodium hydroxide In water pH=13 - 14; Stage #3: acetic acid In ethyl acetate at 31℃;	86%

Upstream product

• 3731-51-9 2-(Aminomethyl)pyridine 
• 50778-59-1 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid chloride 
• 35480-52-5 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid 
• 389082-83-1 2,5-bis(2,2,2-trifluoroethoxy)-α,α-dibromo-α-chloroacetophenone 

Downstream Products

• 54143-56-5 flecainide acetate 

Relevant articles and documents

Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)-benzamide and salts thereof

A process for the preparation of Flecainide acetate, its salts, in particular its pharmaceutically acceptable salts, and intermediates thereof is described wherein 2,5-dibromotoluene is used as a starting material. The method involves a technique for preparing the starting material 2,5-bis(2,2,2-trifluroethoxy)toluene in high yields by reacting 2,5-dibromotoluene with 2,2,2-trifluoroethanol in the presence of a base and a copper-containing catalyst.

α,α-dibromo-α-chloro-acetophenones as synthons

This disclosure relates to the use of α,α-dibromo-α-chloroacetophenone compounds as intermediates for the preparation of aromatic carbonyl compounds, especially aromatic amides. The compound 2,5-bis(2,2,2-trifluoroethoxy)-α,α-dibromo-α-chloroacetophenone is especially useful as an intermediate for the preparation of flecainide, a known pharmaceutical.

Process for the preparation of derivatives of piperidine

Processes for the preparation of the antiarrhythmic agent 2,5-bis(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamide.