881995-73-9

Basic information

• Product Name: Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)-
• Synonyms: Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)-;(R)-Sitagliptin N-Boc-Methyl-Ester IMpurity;(3R)-tert-ButoxycarbonylaMino-4-(2,4,5-trifluoro-phenyl)-butyric acid Methyl ester;Methyl (R)-b-(Boc-amino)-2,4,5-F3-benzenebutanoate
• CAS NO: 881995-73-9
• Molecular Formula: C₁₆H₂₀F₃NO₄
• Molecular Weight: 347.3295096
• EINECS: 1312995-182-4
• Mol File: 881995-73-9.mol
• Article Data: 16

Chemical Properties

• Melting Point: 88-88.5 °C
• Boiling Point: 425.9±45.0 °C(Predicted)
• Appearance: /
• Density: 1.226±0.06 g/cm3(Predicted)
• PKA: 11.23±0.46(Predicted)
• CAS DataBase Reference: Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)-(881995-73-9)
• EPA Substance Registry System: Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)-(881995-73-9)

Safety Data

• Hazardous Substances Data: 881995-73-9(Hazardous Substances Data)

Usage

General Description

Benzenebutanoic acid, b-[[(1,1-dimethylethoxy)carbonyl]amino]-2,4,5-trifluoro-, methyl ester, (bR)- is a chemical compound with potential applications in various industries. It is a methyl ester derivative of benzenebutanoic acid, with a trifluoromethyl group and an amino functional group. Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)- is likely to have properties beneficial for use in pharmaceuticals, agrochemicals, or materials science, due to the presence of the trifluoromethyl group, which can alter the compound's chemical and physical properties, making it potentially valuable in a range of applications. However, further research and testing would be necessary to fully understand and exploit the potential uses of this chemical.

Upstream product

• 881995-70-6 (2Z)-3-amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 881995-69-3 (R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid methyl ester 
• 769195-26-8 4-(2,4,5-trifluoro-phenyl)-3-oxo-butyric acid methyl ester 
• 209995-38-0 (2,4,5-trifluorophenyl)acetic acid 
• 764667-64-3 5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 1151240-93-5 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester 
• 1234321-77-7 (Z)-3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)-2-butenoic acid methyl ester 
• 1253055-94-5 (R)-(-)-mandelic acid salt of (R)-methyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate 
• 1284306-20-2 (S)-methyl 3-(Boc-amino)-4-oxo-4-(2,4,5-trifluorophenyl)butanoate 
• 327-52-6 1-bromo-2,4,5-trifluorobenzene 
• 1310689-94-1 (S)-methyl 4-bromo-3-[(tert-butoxycarbonyl)amino]butanoate 
• 59768-74-0 (S)-2-t-butoxycarbonylaminosuccinic acid 4-methyl ester 
• 136703-59-8 (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoic acid methyl ester 

Downstream Products

• 486460-00-8 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 
• 939964-16-6 (R)-[3-oxo-3-pyrazolidin-1-yl-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl ester 
• 939964-17-7 (R)-[3-oxo-3-(tetrahydropyridazin-1-yl)-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl ester 
• 939964-18-8 (R)-[3-[1,2]diazepan-1-yl-3-oxo-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl ester 
• 939964-27-9 (R)-[3-(2-benzoylcarbamoylpyrazolidin-1-yl)-3-oxo-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl ester 
• 939964-28-0 (R)-[3-oxo-3-(2-(toluene-4-sulfonyl)pyrazolidin-1-yl)-1-(2,4,5-trifluorbenzyl)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 
• 939964-30-4 (R)-[3-(2-benzoyltetrahydropyridazin-1-yl)-3-oxo-1-(2,4,5-trifluorobenzyl)propyl]carbamic acid tert-butyl ester 
• 939964-31-5 tert-butyl (R)-4-(2-benzoyl-1,2-diazepan-1-yl)-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate 
• 486460-23-5 (R)-tert-butyl 4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate 
• 922178-94-7 (S)-3-((tert-butoxycarbonyl)amino)-4-(2,4,5-trifluorophenyl)butanoic acid 
• 1500076-57-2 (R)-tert-butyl (4-(1,1-dioxidothiomorpholine-4-carboxamido)-1-(2,4,5-trifluorophenyl)butan-2-yl)carbamate 
• 1500076-56-1 (R)-tert-butyl (4-(thiomorpholine-4-carboxamido)-1-(2,4,5-trifluorophenyl)butan-2-yl)carbamate 
• 1500076-55-0 (R)-tert-butyl (4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-7-carboxamido)-1-(2,4,5-trifluorophenyl)butan-2-yl)carbamate 

Relevant articles and documents

Nickel-Catalyzed Asymmetric Hydrogenation for the Synthesis of a Key Intermediate of Sitagliptin

Nickel-catalyzed enantioselective hydrogenation of enamines leading to the efficient synthesis of 3-R-Boc-amino-4-(2,4,5-trifluorophenyl)butyric esters, the key intermediate of the blockbuster antidiabetic drug (R)-SITAGLIPTIN, is described. The sitagliptin motifs were isolated in more than 99% yield and with 75–92% ee using the earth-abundant nickel catalyst. Upon chiral resolution with (R)- and (S)-1-phenylethylamines, the partially enantioenriched (R)- and (S)-Boc-3-amino-4-(2,4,5-trifluorophenyl)butanoic acids provided >99.5% ee of the crucial sitagliptin intermediate. The asymmetric hydrogenation protocol was scaled up to 10 g with consistency in yield and ee, and has been reproduced in multiple batches.

A west he row sandbank chiral intermediate and asymmetric synthesis method

The invention relates to a sitagliptin chiral intermediate and an asymmetric synthesis method thereof. The asymmetric synthesis method comprises the steps: with 2,4,5-trifluorophenyl acetic acid as a starting material, carrying out a reduction reaction to obtain 2-(2,4,5-trifluorophenyl)ethanol, then carrying out a reaction with an oxidant, carrying out condensation of the product without separation and (R)-(+)-tert-butyl sulfinamide to obtain corresponding acetal, carrying out a reaction of the obtained product with dialkyl malonate to obtain a key chiral intermediate, hydrolyzing to obtain a corresponding organic amine, carrying out a reaction of the amine with caustic alkali and then acidifying to obtain a corresponding carboxylic acid, then carrying out condensation with 3-(trifluoromethyl)-5,6,7,8- tetrahydro-[1,2,4] triazolo[4,3-a]pyrazine hydrochloride to obtain sitagliptin tert-butyl oxanamide, and finally deprotecting with hydrochloric acid to obtain sitagliptin. The yields of all the steps are all higher, the used reagents are all conventional cheap reagents, no expensive chiral catalysts are used, the reaction conditions are quite mild, and the asymmetric synthesis method is suitable for industrialization.

Sitagliptin intermediate preparation method

The invention relates to the technical field of organic chemistry and especially relates to a sitagliptin intermediate preparation method. The invention provides a compound with a structure shown in the formula 6. The sitagliptin intermediate shown in the formula 8 and prepared from the compound with a structure shown in the formula 6 has high HPLC purity and an ee value of 99% or more.