936630-57-8

Basic information

• Product Name: (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid
• Synonyms: (R)-3-Amino-4-(2,4,5-Trifluorophenyl)butyric Acid Hydrochloride;(R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid;Tert-butyl(R)-1-(methoxycarbonyl)-3-(2,4,5-trifluorophenyl)propan-2-ylcarbamatetert-butyl(R)-1-(methoxycarbonyl)-3-47(2,4,5-trifluorophenyl)propan-2-ylcarbamate;Benzenebutanoic acid, .beta.-aMino-2,4,5-trifluoro-, (.beta.R)-;Sitagliptin-butanoic acid;tert-butyl (R)-1-(Methoxycarbonyl)-3-(2,4,5-trifluorophenyl)propan-2-ylcarbaMate;Benzenebutanoic acid, b-aMino-2,4,5-trifluoro-, (bR)-;Benzenebutanoic acid, β-aMino-2,4,5-trifluoro-, (βR)-
• CAS NO: 936630-57-8
• Molecular Formula: C₁₀H₁₀F₃NO₂
• Molecular Weight: 233.19
• EINECS: 1308068-626-2
• Mol File: 936630-57-8.mol
• Article Data: 19

Chemical Properties

• Melting Point: 217-219 °C(Solv: water (7732-18-5); acetone (67-64-1))
• Boiling Point: 326.6 °C at 760 mmHg
• Flash Point: 151.3 °C
• Appearance: /
• Density: 1.399
• Vapor Pressure: 8.67E-05mmHg at 25°C
• Refractive Index: 1.513
• Storage Temp.: 2-8°C(protect from light)
• PKA: 3.66±0.10(Predicted)
• CAS DataBase Reference: (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid(936630-57-8)
• EPA Substance Registry System: (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid(936630-57-8)

Safety Data

• Hazardous Substances Data: 936630-57-8(Hazardous Substances Data)

Usage

General Description

The chemical (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid is a compound with a molecular structure containing an amino group and a trifluorophenyl group. It is an amino acid derivative with a chiral center, denoted by the "R" in its name. (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid may have potential applications in pharmaceutical research and drug development due to its structural features and potential biological activity. However, further research is needed to fully understand its properties and potential uses in various industries.

InChI:InChI=1/C10H10F3NO2/c11-7-4-9(13)8(12)2-5(7)1-6(14)3-10(15)16/h2,4,6H,1,3,14H2,(H,15,16)/t6-/m1/s1

Synthetic route

C35H27Cl3F3N3NiO3 → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (R)-N-(2-benzoyl-4-chlorophenyl)-1-[(3,4-dichlorophenyl)methyl]-2-pyrrolidinecarboxamide (1644308-43-9)

Conditions	Yield
With hydrogenchloride In ethanol at 50℃;	A 85% B 96%

(R)-3-benzoylamino-4-(2,4,5-trifluorophenyl)butanoic acid methyl ester (1402570-02-8) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With hydrogenchloride In water Reflux;	95%

(S)-methyl 3-(dibenzylamino)-4-oxo-4-(2,4,5-trifluorophenyl)butanoate (1334630-72-6) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Stage #1: (S)-methyl 3-(dibenzylamino)-4-oxo-4-(2,4,5-trifluorophenyl)butanoate With palladium 10% on activated carbon; hydrogen In ethanol at 25℃; for 5h; Stage #2: With hydrogenchloride; water pH=5 - 6;	93.2%

(3R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid ethyl ester (1151240-91-3) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With hydrogenchloride In water at 27℃; for 6h; Reflux;	92%
With lithium hydroxide pH=> 10;

(R)-3-((benzyloxy)amino)-4-(2,4,5-trifluorophenyl)butanoic acid (767352-29-4) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 2068.65 Torr; for 12h;	91%

C18H22F3NO5S → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With hydrogenchloride In methanol at 20℃; pH=1;	91%

methyl (R)-3-(benzyloxyamino)-4-(2,4,5-trifluorophenyl)butanoate (868125-58-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Stage #1: methyl N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(R)-aminobutanoate With palladium on activated charcoal In chloroform for 6h; Autoclave; Stage #2: With hydrogenchloride In water for 6h; pH=4; Reflux;	77%

ethyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate (1151240-92-4) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (S)-ethyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate (1151240-90-2)

Conditions	Yield
With Burkholderia cepacia lipase; water In di-isopropyl ether at 45℃; for 120h; Resolution of racemate; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;	A 43% B n/a

methyl (3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (1S)-(+)-10-camphorsulfonic acid → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; water for 24h;

(S)-1-(2,4,5-trifluorophenyl)pent-4-en-2-amine (1253056-05-1) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With sodium periodate; rhodium(III) chloride hydrate In acetonitrile at 12 - 20℃; for 2h;

(R)-t-butyl 3-(t-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoate (1246961-45-4) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
With trifluoroacetic acid In dichloromethane for 6h;

(2,4,5-trifluorophenyl)-magnesium bromide (502462-00-2) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 2 h / 25 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 5 h / 25 °C 2.2: pH 5 - 6 View Scheme

1-bromo-2,4,5-trifluorobenzene (327-52-6) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium; iodine / tetrahydrofuran / 3 h / 25 °C / Inert atmosphere 2.1: 2 h / 25 °C / Inert atmosphere 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 5 h / 25 °C 3.2: pH 5 - 6 View Scheme

2,4,5-trifluorobenzaldehyde (165047-24-5) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: sodium hydroxide; water / methanol; water / 0.5 h / Cooling with ice 2.1: sodium tetrahydroborate; isopropyl alcohol / chloroform / 0.5 h / 27 °C 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 27 °C 4.1: iodine / 27 °C 5.1: basic alumina / dichloromethane / 2 h / 27 °C 6.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 6.2: polymethylhydrosiloxane (PMHS) / 17 h 6.3: 1 h 7.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme
Multi-step reaction with 8 steps 1.1: sodium hydroxide; water / methanol; water / 0.5 h / Cooling with ice 2.1: sodium tetrahydroborate; isopropyl alcohol / chloroform / 0.5 h / 27 °C 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 27 °C 4.1: iodine / 27 °C 5.1: basic alumina / dichloromethane / 2 h / 27 °C 6.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 6.2: polymethylhydrosiloxane (PMHS) / 17 h 6.3: 1 h 7.1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 8.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

3-(2,4,5-trifluorophenyl)nitroethane → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 27 °C 2.1: iodine / 27 °C 3.1: basic alumina / dichloromethane / 2 h / 27 °C 4.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 4.2: polymethylhydrosiloxane (PMHS) / 17 h 4.3: 1 h 5.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme
Multi-step reaction with 6 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 27 °C 2.1: iodine / 27 °C 3.1: basic alumina / dichloromethane / 2 h / 27 °C 4.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 4.2: polymethylhydrosiloxane (PMHS) / 17 h 4.3: 1 h 5.1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 6.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

1,2,4-trifluoro-5-(2-nitrovinyl)-benzene (913623-45-7) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sodium tetrahydroborate; isopropyl alcohol / chloroform / 0.5 h / 27 °C 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 27 °C 3.1: iodine / 27 °C 4.1: basic alumina / dichloromethane / 2 h / 27 °C 5.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 5.2: polymethylhydrosiloxane (PMHS) / 17 h 5.3: 1 h 6.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme
Multi-step reaction with 7 steps 1.1: sodium tetrahydroborate; isopropyl alcohol / chloroform / 0.5 h / 27 °C 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 27 °C 3.1: iodine / 27 °C 4.1: basic alumina / dichloromethane / 2 h / 27 °C 5.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 5.2: polymethylhydrosiloxane (PMHS) / 17 h 5.3: 1 h 6.1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 7.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

2-hydroxy-3-nitro-4-(2,4,5-trifluoro-phenyl)butyric acid ethyl ester → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: iodine / 27 °C 2.1: basic alumina / dichloromethane / 2 h / 27 °C 3.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 3.2: polymethylhydrosiloxane (PMHS) / 17 h 3.3: 1 h 4.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: iodine / 27 °C 2.1: basic alumina / dichloromethane / 2 h / 27 °C 3.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 3.2: polymethylhydrosiloxane (PMHS) / 17 h 3.3: 1 h 4.1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 5.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

2-acetoxy-3-nitro-4-(2,4,5-trifluorophenyl)butyric acid ethyl ester → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: basic alumina / dichloromethane / 2 h / 27 °C 2.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 2.2: polymethylhydrosiloxane (PMHS) / 17 h 2.3: 1 h 3.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: basic alumina / dichloromethane / 2 h / 27 °C 2.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 2.2: polymethylhydrosiloxane (PMHS) / 17 h 2.3: 1 h 3.1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 4.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

3-nitro-4-(2,4,5-trifluorophenyl)but-2-enoic acid ethyl ester → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: copper (II)-fluoride; 2-(diphenylphosphino)ferrocenylethyldicyclohexylphosphine / toluene / 1 h 1.2: polymethylhydrosiloxane (PMHS) / 17 h 1.3: 1 h 2.1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 3.1: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

3-nitro-4-(2,4,5-trifluorophenyl)butyric acid ethyl ester → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / ethyl acetate / 5 h / 27 °C / 2585.81 Torr 2: hydrogenchloride / water / 6 h / 27 °C / Reflux View Scheme

3-oxo-4-(2,4,5-trifluorophenyl)-butyric acid ethyl ester (1151240-88-8) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (3R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid ethyl ester (1151240-91-3)

Conditions	Yield
With pyridoxal 5'-phosphate; recombinant aminotransferase from Arthobacter sp.; water; isopropylamine In dimethyl sulfoxide at 45℃; for 8h; pH=8.5; Catalytic behavior; Concentration; Time; Enzymatic reaction; Overall yield = 95.87 %Chromat.; enantioselective reaction;	A 34.48 %Chromat. B n/a

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid propyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / acetonitrile / 20 - 45 °C 1.2: 0.5 h / 0 °C 2.1: toluene / 3 h / 100 °C 3.1: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + butyl (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / acetonitrile / 20 - 45 °C 1.2: 0.5 h / 0 °C 2.1: toluene / 3 h / 100 °C 3.1: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + isopropyl (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / acetonitrile / 20 - 45 °C 1.2: 0.5 h / 0 °C 2.1: toluene / 3 h / 100 °C 3.1: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + benzyl (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / acetonitrile / 20 - 45 °C 1.2: 0.5 h / 0 °C 2.1: toluene / 3 h / 100 °C 3.1: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + 2-hydroxyethyl (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / acetonitrile / 20 - 45 °C 1.2: 0.5 h / 0 °C 2.1: 3 h / 100 °C 3.1: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (3R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid ethyl ester (1151240-91-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / acetonitrile / 20 - 45 °C 1.2: 0.5 h / 0 °C 2.1: toluene / 3 h / 100 °C 3.1: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid propyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 3 h / 100 °C 2: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + butyl (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 3 h / 100 °C 2: water; recombinant aminotransferase from Arthobacter sp.; pyridoxal 5'-phosphate; isopropylamine / dimethyl sulfoxide / 8 h / 45 °C / pH 8.5 / Enzymatic reaction View Scheme

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) → (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid hydrochloride (1204818-19-8)

Conditions	Yield
With hydrogenchloride In ethanol optical yield given as %ee;	100%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + 1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) → C14H13F3N2O4

Conditions	Yield
With dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 2h; Reflux;	95%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + di-tert-butyl dicarbonate (24424-99-5) → (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (486460-00-8)

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 20℃;	91%
Stage #1: (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid With lithium hydroxide In 1,4-dioxane; water at 0 - 30℃; Stage #2: di-tert-butyl dicarbonate In 1,4-dioxane; water at 25 - 30℃;	91%
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 24h;	91%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (486460-21-3) → sitagliptin (486460-32-6)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol In ethanol; dichloromethane at 10 - 25℃; for 3h;	86%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (486460-00-8) → C25H26F6N2O5

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In acetonitrile at 20 - 30℃; Reagent/catalyst;	70%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + sitagliptin (486460-32-6) → C26H23F9N6O2

Conditions	Yield
With dmap; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 80 - 90℃; for 24h;	65%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + di-tert-butyl dicarbonate (24424-99-5) → C20H26F3NO6

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h;	60%

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C7H14N2O → C17H22F3O2N3 + C17H22F3O2N3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In acetonitrile

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C15H22N2O2 → C25H30F3O3N3 + C25H30F3O3N3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In acetonitrile

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C8H13N2OF3 → C18H21F6O2N3 + C18H21F6O2N3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In acetonitrile

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + 1-tert-butyl-1,4-diazepan-2-one → C20H28F3O2N3 + C20H28F3O2N3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In acetonitrile

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C9H16N2O (842104-09-0) → C19H24N3O2F3 + C19H24N3O2F3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C7H14N2O (842103-96-2) → C17H22N3O2F3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C7H14N2O (842103-82-6) → C17H22N3O2F3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C7H14N2O → C17H22N3O2F3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) + C9H16N2O → C19H24F3O2N3 + C19H24F3O2N3

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In acetonitrile

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) → ((R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)piperazin-2-one)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydrogencarbonate / methanol / 6 h / 0 - 20 °C 2.1: 4-methyl-morpholine; isobutyl chloroformate / dichloromethane / 1.17 h / 0 °C 2.2: 1 h / 0 °C 3.1: hydrogenchloride; sodium hydrogencarbonate / dichloromethane; isopropyl alcohol View Scheme

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) → (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(t-butoxymethyl)piperazin-2-one L-tartrate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate / methanol / 6 h / 0 - 20 °C 2.1: 4-methyl-morpholine; isobutyl chloroformate / dichloromethane / 1.17 h / 0 °C 2.2: 1 h / 0 °C 3.1: hydrogenchloride; sodium hydrogencarbonate / dichloromethane; isopropyl alcohol 4.1: isopropyl alcohol; ethanol; water; acetone / 0.5 h View Scheme

(R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid (936630-57-8) → t-butyl (R)-4-[(R)-2-(t-butoxymethyl)-3-oxopiperazin-1-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / methanol / 6 h / 0 - 20 °C 2.1: 4-methyl-morpholine; isobutyl chloroformate / dichloromethane / 1.17 h / 0 °C 2.2: 1 h / 0 °C View Scheme

Upstream product

• 1151240-92-4 ethyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate 
• 1253056-05-1 (S)-1-(2,4,5-trifluorophenyl)pent-4-en-2-amine 
• 1246961-45-4 (R)-t-butyl 3-(t-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoate 
• 1176895-65-0 2-(2,4,5-trifluorophenyl)acetyl chloride 
• 1283583-85-6 racemic 3-amino-4-(2,4,5-trifluorophenyl)butanoic acid 
• 868125-58-0 methyl N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(R)-aminobutanoate 
• 1152439-73-0 2,2-dimethyl-5-[2-(2,4,5-trifluorophenyl)acetyl]-[1,3]dioxane-4,6-dione 
• 1402570-02-8 (R)-3-benzoylamino-4-(2,4,5-trifluorophenyl)butanoic acid methyl ester 
• 769195-26-8 4-(2,4,5-trifluoro-phenyl)-3-oxo-butyric acid methyl ester 

Downstream Products

• 1204818-19-8 (R)-3-amino-4-phenyl(2,4,5-trifluorophenyl)butanoic acid hydrochloride 
• 1222102-51-3 (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(t-butoxymethyl)piperazin-2-one L-tartrate 
• 486460-32-6 sitagliptin 
• 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 
• 654671-77-9 sitagliptin phosphate monohydrate 

Relevant articles and documents

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