936630-57-8

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
(R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid is used as a research compound for exploring its potential biological activity and interactions with various biological targets. Its unique molecular structure, including the trifluorophenyl group and the chiral center, may contribute to its ability to modulate specific biological pathways or interact with certain receptors, making it a valuable tool in the discovery and development of new therapeutic agents.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, (R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid serves as a building block or a starting material for the synthesis of more complex molecules with potential therapeutic applications. Its structural features can be exploited to design and optimize new drug candidates with improved pharmacological properties, such as enhanced potency, selectivity, and reduced side effects.
Used in Chemical Synthesis:
(R)-3-Amino-4-(2,4,5-trifluorophenyl)butyric acid can be utilized as a synthetic intermediate in the preparation of other organic compounds, particularly those with pharmaceutical or biological relevance. Its reactivity and functional groups can be employed in various chemical reactions, such as amide formation, acylation, or substitution reactions, to generate a diverse range of target molecules with potential applications in different 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

• 767352-29-4 (R)-3-((benzyloxy)amino)-4-(2,4,5-trifluorophenyl)butanoic acid 
• 502462-00-2 (2,4,5-trifluorophenyl)-magnesium bromide 
• 327-52-6 1-bromo-2,4,5-trifluorobenzene 
• 1334630-72-6 (S)-methyl 3-(dibenzylamino)-4-oxo-4-(2,4,5-trifluorophenyl)butanoate 
• 1151240-88-8 3-oxo-4-(2,4,5-trifluorophenyl)-butyric acid ethyl ester 
• 1152439-73-0 2,2-dimethyl-5-[2-(2,4,5-trifluorophenyl)acetyl]-[1,3]dioxane-4,6-dione 
• 868125-58-0 methyl N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(R)-aminobutanoate 
• 1283583-85-6 racemic 3-amino-4-(2,4,5-trifluorophenyl)butanoic acid 
• 1176895-65-0 2-(2,4,5-trifluorophenyl)acetyl chloride 

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 

Relevant academic research and scientific papers

Preparation method of 1,3-dicarbonyl compound and intermediate of the 1,3-dicarbonyl compound

The invention discloses a preparation method of a 1,3-dicarbonyl compound and an intermediate of the 1,3-dicarbonyl compound, and particularly discloses a preparation method of a compound as shown ina formula I. The preparation method comprises the following step: in a solvent, performing an elimination reaction as shown in the specification on a compound as shown in a formula II to obtain the compound as shown in the formula I, wherein R is a tert-butoxy group, a methoxy group, an ethoxy group or a methyl group. The preparation method disclosed by the invention is relatively low in cost andbeneficial to industrial production.

Preparation method of 1-morpholinyl-4-(2,4,5-trifluorophenyl)butane-1,3-dione

The invention discloses a preparation method of 1-morpholinyl-4-(2,4,5-trifluorophenyl)butane-1,3-dione, and belongs to the technical field of organic synthesis. The preparation method comprises the following step: under the action of a metal chelating agent and an alkali, carrying out a reaction of the following formula on a compound 2 and a compound 3 in an organic solvent to obtain a compound 1. The preparation method disclosed by the invention is high in yield, simple in post-treatment, simple, feasible, mild in reaction condition and suitable for industrial production.

A west geleg sandbank intermediate biological synthesis method (by machine translation)

The invention discloses a west geleg sandbank intermediate biological synthesis method, namely in order to 4 - (2, 4, 5 - trifluoro methyl) uracil as the substrate under the action, by the one-pot preparation, Or, 4 - (2, 4, 5 - trifluoro methyl) uracil enzyme preparation obtained the situation that the (R)- 3 - carbamoyl amino - 4 - (2, 4, 5 - trifluorophenyl) butanoic acid, after separation, then the role of the enzyme or acid producing the (R)- 3 - amino - 4 - (2, 4, 5 - trifluorophenyl) butanoic acid, The west geleg sandbank intermediate the biological synthesis of simple process, without special request to device, to obtain a high EE value of the product, is suitable for industrial production. (by machine translation)

Preparation method of medication sitagliptin for treating diabetes

The invention provides a preparation method of sitagliptin with a shorter route. In the presence of a chiral ligand, reductive amination is performed by borohydride to obtain a chiral amine compound,then activation of a carboxyl group is performed by N-hydroxysuccinimide to reduce the occurrence of side reactions, and obtain a sitagliptin product with a high yield and high purity, the reaction raw materials are cheap and easy to obtain, the reaction process is easy to operate, the yield of each step is high, the purity of the product is high, the production cost is reduced, and industrial production is facilitated.

Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β- and γ-Amino Acids Using Transaminase

A recyclable glutamate amine donor system employing transaminase (TA), glutamate dehydrogenase (GluDH) and mutant formate dehydrogenase (FDHm) was developed, wherein amine donor Glu was regenerated using GluDH and thereby circumvented the inhibition of TA by α-ketoglutarate. Various enantiopure β-, γ-amino acids, and amines were successfully synthesized with high conversions and excellent enantiomeric excess using this system.

Method for synthesizing sitagliptin and intermediate thereof through biological catalysis

The invention provides a method for synthesizing sitagliptin and an intermediate thereof through biological catalysis, and particularly provides compounds as shown in formula I and a formula II, or pharmaceutically acceptable salt thereof, polypeptide capable of synthesizing a compound as shown in the formula I to produce a compound as shown in the formula II, nucleic acid coding the polypeptide,and a vector and a cell containing the nucleic acid. In addition, the invention further provides a method for producing the compound as shown in the formula II and sitagliptin through the polypeptideand the compound as shown in the formula I, and a preparation method for preparing the polypeptide.

Preparation method of 3-aminopropanol or 3-aminopropionic acid derivative

The invention provides a preparation method of an optically active 3-aminopropanol or 3-aminopropionic acid derivative, and belongs to the technical field of organic synthesis. A compound having a structure as shown in a formula II and a formula III is used as a raw material, and the optically active 3-aminopropanol or 3-aminopropionic acid derivative is obtained through four basic steps, namely dehydration condensation, hydrogenation reduction, reduction and hydrolysis. The raw materials adopted in the preparation method are easy to obtain and low in cost; as a chiral phosphine-transitional metal catalyst is used in the hydrogenation reduction reaction, the optically active 3-aminopropanol or 3-aminopropionic acid derivative is efficient, high in selectivity, low in cost and suitable forlarge-scale production. Compared with existing chemical resolution and chiral introduction, the asymmetric hydrogenation synthesis method provided by the invention only produces one chiral product, ishigh in yield, and has relatively high advantages in economy and raw material utilization rate.

Chiral synthesis method for chiral beta-amino acid and synthesis method for medicinal intermediate

The invention relates to a chiral synthesis method for chiral beta-amino acid. The chiral synthesis method comprises the following steps: reacting a compound shown in formula (II) with an acylation reagent to prepare anhydride intermediate reaction liquid under the action of alkali; adding Meldrum's acid into the anhydride intermediate reaction liquid, and performing reaction to generate a compound shown in formula (III); reacting the compound shown in formula (III) with a compound shown in formula (IV) to generate a compound shown in formula (V); reducing the compound shown in formula (V) to generate a compound shown in formula (VI); performing acidic hydrolysis on the compound shown in formula (VI) to generate a compound shown in formula (I), i.e., the chiral beta-amino acid. The chiral synthesis method has the advantages of convenience for synthesis, low cost and simple process, and compared with a disclosed preparation method, is more suitable for industrial production.

Purpose of compound for preparing Sitagliptin and Sitagliptin preparation method

The invention provides a compound shown by a formula I, a purpose of a stereoisomer, a geometrical isomer, a tautomer, an oxynitride, a hydrate, a solvate, a metabolite, a pharmacologically acceptable salt or prodrug of the compound in Sitagliptin preparation, and a Sitagliptin preparation method. The formula I is shown in the description, wherein R1 is a substitutional group containing the hydroxyl group. The compound shown by the formula I or the stereoisomer, the geometrical isomer, the tautomer, the oxynitride, the hydrate, the solvate, the metabolite, the pharmacologically acceptable salt or the prodrug of the compound shown by the formula I has high water solubility, and is used for obtaining a chiral amino intermediate to further obtain the Sitagliptin. Compared with the prior art, the compound has the advantages that the amino group conversion rate is greatly improved; the yield of the Sitagliptin is also greatly improved.

Substrate screening of amino transaminase for the synthesis of a sitagliptin intermediate

We reported herein a new enzymatic route to synthesize a sitagliptin intermediate using an aminotransferase. Substrate profile indicated that hydroxyethyl-3-oxo-4-(2,4,5-trifluorophenyl)butanoate, among 11 analogs, showed the best biocatalytic performance, partially due to its best solubility in the enzymatic system. The corresponding amino esters showing strong product inhibition on the reaction, were inclined to autohydrolyze, thus driving the reaction forward, which indicated the contribution of the rapid hydrolysis of hydroxyethyl ester to the biocatalytic performance. The reaction was performed at 100?mM with 82% conversion in 24?h. The amino ester product was further transformed to Boc-(R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid, the key intermediate of sitagliptin.