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

• 352223-25-7 2-(2,4-difluoro-5-nitrophenyl)acetic acid 
• 243139-71-1 1-(chloromethyl)-2,4,5-trifluorobenzene 
• 220141-74-2 2-(2,4,5-trifluorophenyl)acetonitrile 
• 102492-71-7 α,2,4-trichloro-5-nitrotoluene 
• 94-99-5 2,4-Dichlorobenzyl chloride 
• 95-73-8 2,4-dichlorotoluene 
• 6306-60-1 2,4-Dichlorophenylacetonitrile 
• 24789-93-3 2,4-dichloro-5-nitrobenzeneacetonitrile 
• 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 

Downstream Products

• 764667-65-4 1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione 
• 1169707-30-5 (3R)-3-[[(1R)-1-phenylethyl]amino]-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one 
• 769195-20-2 (3R)-3-[[(1S)-1-carboxamidophenylmethyl]amino]-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one 
• 823817-55-6 (S)-Sitagliptin 
• 1152439-73-0 2,2-dimethyl-5-[2-(2,4,5-trifluorophenyl)acetyl]-[1,3]dioxane-4,6-dione 
• 251366-49-1 α-bromo-(2,4,5-trifluorophenyl)acetic acid 
• 29270-33-5 2-bromo-2-(4-fluorophenyl)acetic acid 
• 881995-70-6 (2Z)-3-amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester 
• 486460-00-8 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 
• 939964-31-5 tert-butyl (R)-4-(2-benzoyl-1,2-diazepan-1-yl)-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate 
• 939964-30-4 (R)-[3-(2-benzoyltetrahydropyridazin-1-yl)-3-oxo-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl ester 
• 939964-29-1 (R)-[3-(2-benzoylpyrazolidin-1-yl)-3-oxo-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl 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.

Preparation method of 2,4,5-trifluorophenylacetic acid

The invention belongs to the technical field of preparation of drug intermediates, and discloses a preparation method of 2,4,5-trifluorophenylacetic acid, wherein the preparation method comprises the steps: step 1, reacting raw materials, a quaternary ammonium salt catalyst, sulfolane and potassium fluoride to obtain a first intermediate; step 2, carrying out hydrogenation catalytic reaction on the first intermediate to obtain a second intermediate; step 3, carrying out salt forming reaction on the second intermediate and a fluorinating reagent, quenching, and carrying out diazotization reaction on the second intermediate and a sodium nitrite aqueous solution to obtain diazonium salt; step 4, carrying out high-temperature cracking on the diazonium salt, to obtain 2,4,5-trifluorotoluene; and step 5 to step 7, carrying out halogenation, cyanidation and hydrolysis reactions on 2,4,5-trifluorotoluene in sequence, and thus obtaining 2,4,5-trifluorophenylacetic acid. The raw materials adopted by the method are easy to obtain and low in cost, the yield of the corresponding product obtained in each step is high, and large-scale production of the 2,4,5-trifluorophenylacetic acid is facilitated.

Preparation method of 2,4,5-trifluorophenylacetic acid

The invention provides a preparation method of 2,4,5-trifluorophenylacetic acid. 1,2,4-trifluorobenzene as a raw material and glycolide are catalyzed by a Lewis acid to obtain a final product that issitagliptin intermediate 2,4,5-trifluorophenylacetic acid. The method is mild in reaction condition, and convenient to operate, raw materials are cheap and easily available, steps are simple, and operability is high. High-pressure reaction equipment is not used in the production process, harmful and toxic reagents are not involved, the method has the advantages of being high in safety and environmentally friendly, the obtained 2,4,5-trifluorophenylacetic acid is high in purity, a more valuable synthetic route is provided for preparation of sitagliptin, good social benefits and economic benefits can be brought, and the economic value potential is large.