209995-38-0

Basic information

• Product Name: 2,4,5-Trifluorophenylacetic acid
• Synonyms: RARECHEM AL BO 0510;2,4,5-TRIFLUOROPHENYLACETIC ACID;2,4,5-Trifluorophenylaceticacid97%;2,4,5-Trifluorophenylacetic acid ,99%;2,4,5-Trifluoropheny;2,4,5-trifluoropheylacetic acid;5-Trifluorophenylacetic acid;2, 4, 5-Trifluorobenzeneacetic acid
• CAS NO: 209995-38-0
• Molecular Formula: C₈H₅F₃O₂
• Molecular Weight: 190.12
• EINECS: 466-070-3
• Product Categories: Acetics acid and esters;Benzene series;Phenylacetic acid;Miscellaneous;C8;Carbonyl Compounds;Carboxylic Acids
• Mol File: 209995-38-0.mol
• Article Data: 27

Chemical Properties

• Melting Point: 121-125°C
• Boiling Point: 255 °C at 760 mmHg
• Flash Point: 108 °C
• Appearance: white or off white power
• Density: 1.468 g/cm³
• Vapor Pressure: 0.00866mmHg at 25°C
• Refractive Index: 1.488
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 3.78±0.10(Predicted)
• CAS DataBase Reference: 2,4,5-Trifluorophenylacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4,5-Trifluorophenylacetic acid(209995-38-0)
• EPA Substance Registry System: 2,4,5-Trifluorophenylacetic acid(209995-38-0)

Safety Data

• Hazard Codes: Xi
• Statements: 37/38-41
• Safety Statements: 26-39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 209995-38-0(Hazardous Substances Data)

Usage

Chemical Properties

White to light brown solid

Uses

2,4,5-Trifluorobenzeneacetic Acid is used in the synthesis of EGFR/ErbB-2-kinase inhibitors. Also used in the synthesis of new imidazopyrazinone derivatives as potnetial dipeptidyl peptidase IV inhibitors.

Application

2,4,5-Trifluorophenylacetic acid is used to synthesize the intermediate of sitagliptin, a new drug for the treatment of type II diabetes. sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor newly launched by Merck. It has good curative effect, small side effects, good safety and tolerance in treating type II diabetes.

Preparation

synthesis of 2,4,5-trifluorophenylacetic acid: A 100 mL flask was charged 10.0 g of 2,4,5-trifluoromandelic acid, 23.9 g of H3PO3 (6 eq.), 0.73 g of Nal (0.1 eq.) and 0.47 g (0.10 eq.) of MSA. The obtained mixture was stirred at 95-105°C for 24 hrs. Once the conversion is completed (by HPLC; conversion > 99%, typically achieved after 24 hours), the mixture is cooled to room temperature, and 20 mL of methyl tert-butyl ether were added and then 20 mL of water where added. The obtained mixture was stirred for 5 min, then the organic layers were separated. Then 10 mL of methyl tert-butyl ether was added to the aqueous layers, stirred for 5 min, then the phase were separated. The organic layers were combined. The combined organic layers were concentrated under vacuum at 35°C, to provide crude 2,4,5-trifluorophenylacetic acid(TFPAA). To the obtained crude TFPAA was recrystallized from toluene, to obtain TFPAA, as a white crystals, 6.4 g, molar yield 69.5%, chemical purity of HPLC 99.47% A/A%

InChI:InChI=1/C8H5F3O2/c9-5-3-7(11)6(10)1-4(5)2-8(12)13/h1,3H,2H2,(H,12,13)

Upstream product

• 1256470-41-3 ethyl 2-(2,4,5-trifluorophenyl)acetate 
• 327-52-6 1-bromo-2,4,5-trifluorobenzene 
• 446-35-5 2,4-Difluoronitrobenzene 
• 611-06-3 2,4-dichloronitrobenzene 
• 541-73-1 1,3-Dichlorobenzene 
• 367-25-9 2,4-difluorophenylamine 
• 875664-57-6 4,5-difluoro-2-methylaniline 
• 127371-50-0 1,2-difluoro-4-methyl-5-nitrobenzene 
• 7494-45-3 1,2-dichloro-4-methyl-5-nitrobenzene 
• 220141-74-2 2-(2,4,5-trifluorophenyl)acetonitrile 
• 64-19-7 acetic acid 
• 887267-34-7 2,4,5-Trifluoro-toluene 
• 24789-93-3 2,4-dichloro-5-nitrobenzeneacetonitrile 
• 6306-60-1 2,4-Dichlorophenylacetonitrile 

Downstream Products

• 764667-64-3 5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 1036273-20-7 2,4,5-trifluorophenylacetic acid methyl ester 
• 881995-70-6 (2Z)-3-amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester 
• 769195-26-8 4-(2,4,5-trifluoro-phenyl)-3-oxo-butyric acid methyl ester 

Relevant articles and documents

Preparation method of 2, 4, 5-trifluorophenylacetic acid

The invention provides a preparation method of 2, 4, 5-trifluorophenylacetic acid. The method comprises the following steps: 1) reacting 2, 4, 5-trifluorobromobenzene with metal magnesium to obtain 2, 4, 5-trifluorophenyl magnesium bromide; 2) reacting 2, 4, 5-trifluorophenyl magnesium bromide with halogenated acetate to prepare an intermediate A; 3) hydrolyzing the intermediate A in an alkaline solution or an acidic solution to obtain 2, 4, 5-trifluorophenylacetic acid. The structure of the intermediate A is shown as the following structure, wherein R represents a C1-C10 alkyl group. The preparation method of 2, 4, 5-trifluorophenylacetic acid provided by the invention has the advantages of simple process flow, low cost, environmental friendliness and mild conditions.

Novel preparation method of 2, 4, 5-trifluorophenylacetic acid

The invention discloses a novel preparation method of 2, 4, 5-trifluorophenylacetic acid, which belongs to the technical field of preparation of medical intermediates, and comprises the following preparation steps: carrying out nitration reaction on sulfuric acid and m-dichlorobenzene to obtain an intermediate II; adding the intermediate II, a phase transfer catalyst and potassium fluoride into an aprotic solvent to obtain an intermediate III; performing hydrogenation reaction on the intermediate III to obtain an intermediate IV; carrying out diazotization reaction on the intermediate IV, nitrosyl sulfuric acid and sodium fluoborate to obtain an intermediate V; performing cracking reaction on the intermediate V to obtain an intermediate VI; carrying out reduction reaction on the intermediate VI, and then carrying out bromination reaction on the intermediate VI and liquid bromine to obtain an intermediate VII; subjecting the intermediate VII to a substitution reaction with diethyl malonate, and obtaining 2, 4, 5-trifluorophenylacetic acid after hydrolysis and purification. A novel synthesis route is provided, the problem that technological operation is tedious is solved, the requirements for reaction and operation conditions are low, anhydrous and oxygen-free reaction conditions are not needed, the method is suitable for industrial production, and the yield and purity are greatly improved.

Synthesis method of 2,4,5-trifluorophenylacetic acid

The invention discloses a synthesis method of 2,4,5-trifluorophenylacetic acid. 2,4,5-trifluorobromobenzene is used as starting material and condensed with diethyl malonate under the action of magnesium ethylate to obtain 2,4,5-trifluoro-diethyl malonate, 2,4,5-trifluoro-diethyl malonate is hydrolyzed under acidic conditions to obtain 2,4,5-trifluorophenylacetic acid. The invention is simple and easy to operate, the raw materials are cheap and easily available, the total reaction yield is high, and the invention is suitable for industrial production.