111991-20-9

Usage

Uses

Used in Pharmaceutical Industry:
2-(2,4,5-Trifluorophenyl)acetaldehyde is used as a key intermediate in the synthesis of EGFR/ErbB-2-kinase inhibitors. These inhibitors play a crucial role in the development of targeted cancer therapies, as they help in modulating the activity of specific protein kinases involved in cell signaling and tumor growth.
Additionally, 2-(2,4,5-Trifluorophenyl)acetaldehyde is used as a starting material in the synthesis of new imidazopyrazinone derivatives. These derivatives have potential applications as dipeptidyl peptidase IV (DPP-IV) inhibitors, which are important in the treatment of type 2 diabetes and other metabolic disorders.

Synthetic route

2-(2,4,5-trifluorophenyl)ethanol (883267-70-7) → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
With manganese(IV) oxide In toluene for 8h; Reagent/catalyst; Solvent; Reflux;	75%

1,2,4-trifluoro-5-(2-methoxyethenyl)benzene → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 20℃; for 6h;
With hydrogenchloride In tetrahydrofuran; water at 0 - 30℃; for 2h;	2 g
With hydrogenchloride In 1,4-dioxane at 20℃; for 6h;

2,4,5-trifluorobenzaldehyde (165047-24-5) → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 0 - 20 °C 1.2: 48 h / 20 °C 2.1: hydrogenchloride / tetrahydrofuran; water / 2 h / 0 - 30 °C View Scheme

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid / methanol / 3 h / Heating 1.2: 20 °C / Cooling with ice 2.1: manganese(IV) oxide / toluene / 8 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / 3 h / Reflux 2.1: sodium tetrahydroborate / tetrahydrofuran / 1 h 2.2: 5 h View Scheme

2,4,5-trifluorophenylacetic acid methyl ester (1036273-20-7) → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
Stage #1: 2,4,5-trifluorophenylacetic acid methyl ester With sodium tetrahydroborate In tetrahydrofuran for 1h; Stage #2: With pyridinium chlorochromate In dichloromethane for 5h;

1-chloro-2-(2,4,5-trifluorophenyl)ethyl acetate → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
With hydrogenchloride; Aliquat 336 In water; acetone at 25 - 30℃; for 24h; Reagent/catalyst;

2,4,5-trifluoroaniline (367-34-0) → 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 1 h 1.2: 0 °C 1.3: 0 °C 2.1: Aliquat 336; hydrogenchloride / water; acetone / 24 h / 25 - 30 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R,E)-2-methyl-N-[2-(2,4,5-trifluorophenyl)ethylidene]propane-2-sulfinamide

Conditions	Yield
With pyridinium p-toluenesulfonate; sodium sulfate In dichloromethane at 20℃; for 16h;	96%

malonic acid (141-82-2) + 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → C10H7F3O2

Conditions	Yield
With piperidine In toluene Temperature; Solvent; Reagent/catalyst; Knoevenagel Condensation; Reflux;	94.3%

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) + L-Phenylalaninol (3182-95-4) + allyltributylstanane (24850-33-7) → C20H22F3NO

Conditions	Yield
Stage #1: 2-(2,4,5-trifluorophenyl)acetaldehyde; L-Phenylalaninol With magnesium(I) iodide In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: allyltributylstanane In dichloromethane at 20℃; Reagent/catalyst; Solvent; Inert atmosphere;	82%

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → (2,4,5-trifluorophenyl)acetic acid (209995-38-0)

Conditions	Yield
With sodium chlorite; water at 0 - 5℃; for 6h; Reagent/catalyst;	80%

tert-butyl diethylphosphonoacetate (27784-76-5) + 2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → tert-butyl (E)-4-(2',4',5'-trifluorophenyl)but-2-enoate (1380521-84-5)

Conditions	Yield
Stage #1: tert-butyl diethylphosphonoacetate With methylmagnesium bromide In tetrahydrofuran; diethyl ether for 0.25h; Stage #2: 2-(2,4,5-trifluorophenyl)acetaldehyde In tetrahydrofuran; diethyl ether for 15h; Wadsworth-Emmons reaction; Reflux; optical yield given as %de; diastereoselective reaction;	74%

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) + S-tert-butylsulfinimide (146374-27-8) → 2-methylpropane-2-sulfinic acid [2-(2,4,5-trifluorophenyl)-eth-(Z)-ylidene]amide

Conditions	Yield
toluene-4-sulfonic acid In toluene Reflux;

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → sitagliptin phosphate

Conditions	Yield
Multi-step reaction with 6 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux 4.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / chloroform / 16 h / 20 °C 5.1: 30% w/w Pd(OH)2/C; hydrogen / methanol / 24 h / 3800.26 Torr 6.1: phosphoric acid / ethanol / 0.5 h / 80 °C View Scheme
Multi-step reaction with 6 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux 4.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / chloroform / 16 h / 20 °C 5.1: 20 wt.% Pd(OH)2 on activated carbon; hydrogen / methanol / 24 h / 3800.26 Torr 6.1: phosphoric acid / ethanol / 0.5 h / 80 °C View Scheme
Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 12 h / Reflux 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -20 °C 2.2: 2 h / -20 °C 3.1: hydrogenchloride / water / 12 h / Reflux 3.2: 0.5 h / Cooling with ice 3.3: 20 °C 4.1: hydrogen; 5%-palladium/activated carbon; acetic acid / methanol / 48 h / 50 °C / 19001.3 Torr 5.1: phosphoric acid / ethanol / 0.5 h / Reflux View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → tert-butyl (R,R)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4-(2',4',5'-trifluorophenyl)butanoate (1380521-85-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → tert-butyl (R,R)-3-[N-benzyl-N-(α-methyl-p-methoxybenzyl)amino]-4-(2',4',5'-trifluorophenyl)butanoate (1380521-86-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → C25H24F3NO2*ClH (1380521-87-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → (R,R)-N-benzyl-N-(α-methylbenzyl)-1-(2',4',5'-trifluorophenyl)-4-oxo-4-{3''-(trifluoromethyl)-5'',6''-dihydro-1'',2'',4''-triazolo[4,3-α]pyrazin-7''(8''H)-yl}butan-2-amine (1380521-88-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux 4.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / chloroform / 16 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / 12 h / Reflux 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -20 °C 2.2: 2 h / -20 °C 3.1: hydrogenchloride / water / 12 h / Reflux 3.2: 0.5 h / Cooling with ice 3.3: 20 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → C26H26F3NO3*ClH

Conditions	Yield
Multi-step reaction with 3 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → (R)-N-benzyl-1-(2',4',5'-trifluorophenyl)-4-oxo-4-{3''-(trifluoromethyl)-5'',6''-dihydro-1'',2'',4''-triazolo[4,3-α]pyrazin-7''(8''H)-yl}butan-2-amine (1393363-87-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux 4.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / chloroform / 16 h / 20 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → sitagliptin (486460-32-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux 4.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / chloroform / 16 h / 20 °C 5.1: 30% w/w Pd(OH)2/C; hydrogen / methanol / 24 h / 3800.26 Torr View Scheme
Multi-step reaction with 5 steps 1.1: methylmagnesium bromide / tetrahydrofuran; diethyl ether / 0.25 h 1.2: 15 h / Reflux 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 2 h / -78 °C 3.1: hydrogenchloride / water / 6 h / Reflux 4.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / chloroform / 16 h / 20 °C 5.1: 20 wt.% Pd(OH)2 on activated carbon; hydrogen / methanol / 24 h / 3800.26 Torr View Scheme
Multi-step reaction with 6 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 7 h / 0 °C 3: palladium diacetate; triphenylphosphine; triethylamine; formic acid / ethyl acetate / 3 h / Reflux 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C 5: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 0 - 20 °C 6: hydrogenchloride; water / methanol / 4 h / 20 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → diethyl 2-{(R)-1-[((R)-tert-butylsulfinyl)amino]-2-(2,4,5-trifluorophenyl)ethyl}malonate

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 4 h / 0 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → diethyl 2-{(R)-1-[((R)-tert-butylsulfinyl)amino]-2-(2,4,5-trifluorophenyl)ethyl}malonate + C19H26F3NO5S

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: potassium carbonate; 18-crown-6 ether / neat (no solvent) / 1 h / 0 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → ethyl (R)-3-[((R)-tert-butylsulfinyl)amino]-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: potassium carbonate; 18-crown-6 ether / neat (no solvent) / 1 h / 0 °C 3: hydrogenchloride / methanol; water / 20 °C View Scheme
Multi-step reaction with 3 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 4 h / 0 °C 3: hydrogenchloride / methanol; water / 20 °C View Scheme
Multi-step reaction with 3 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 7 h / 0 °C 3: palladium diacetate; triphenylphosphine; triethylamine; formic acid / ethyl acetate / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: magnesium sulfate; pyridinium p-toluenesulfonate / dichloromethane / 24 h / Reflux 2.1: chloro-trimethyl-silane; zinc; copper(l) chloride / tetrahydrofuran / 0.33 h / 50 °C 2.2: 2.33 h / -5 - 60 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → 1-allyl-3-methyl {(R)-1-[((R)-tert-butylsulfinyl)amino]-2-(2,4,5-trifluorophenyl)ethyl}malonate

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 4 h / 0 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → 1-allyl-3-ethyl {(R)-1-[((R)-tert-butylsulfinyl)amino]-2-(2,4,5-trifluorophenyl)ethyl}malonate

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 7 h / 0 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → diallyl {(R)-1-[((R)-tert-butylsulfinyl)amino]-2-(2,4,5-trifluorophenyl)ethyl}malonate

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 4 h / 0 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → (R)-3-[((R)-tert-butylsulfinyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: potassium carbonate; 18-crown-6 ether / neat (no solvent) / 1 h / 0 °C 3: hydrogenchloride / methanol; water / 20 °C 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C View Scheme
Multi-step reaction with 4 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 4 h / 0 °C 3: hydrogenchloride / methanol; water / 20 °C 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C View Scheme
Multi-step reaction with 4 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 7 h / 0 °C 3: palladium diacetate; triphenylphosphine; triethylamine; formic acid / ethyl acetate / 3 h / Reflux 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C View Scheme
Multi-step reaction with 3 steps 1.1: magnesium sulfate; pyridinium p-toluenesulfonate / dichloromethane / 24 h / Reflux 2.1: chloro-trimethyl-silane; zinc; copper(l) chloride / tetrahydrofuran / 0.33 h / 50 °C 2.2: 2.33 h / -5 - 60 °C 3.1: lithium hydroxide / water; methanol / 2 h / 0 - 20 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → (R)-2-methyl-N-((R)-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-yl)propane-2-sulfinamide (1349649-83-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 7 h / 0 °C 3: palladium diacetate; triphenylphosphine; triethylamine; formic acid / ethyl acetate / 3 h / Reflux 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C 5: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: potassium carbonate; 18-crown-6 ether / neat (no solvent) / 1 h / 0 °C 3: hydrogenchloride / methanol; water / 20 °C 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C 5: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2: sodium iodide; potassium carbonate / neat (no solvent) / 4 h / 0 °C 3: hydrogenchloride / methanol; water / 20 °C 4: sodium hydroxide; water / tetrahydrofuran / 2 h / 40 °C 5: triethylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: magnesium sulfate; pyridinium p-toluenesulfonate / dichloromethane / 24 h / Reflux 2.1: chloro-trimethyl-silane; zinc; copper(l) chloride / tetrahydrofuran / 0.33 h / 50 °C 2.2: 2.33 h / -5 - 60 °C 3.1: lithium hydroxide / water; methanol / 2 h / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0.17 h / 0 - 20 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → tert-butyl (R)-3-[((R)-tert-butylsulfinyl)amino]-4-(2,4,5-trifluorophenyl)butanoate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: pyridinium p-toluenesulfonate; sodium sulfate / dichloromethane / 16 h / 20 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 3 h / -78 °C View Scheme

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-2-methyl-N-(2-(2,4,5-trifluorophenyl)ethylidene)propane-2-sulfinamide

Conditions	Yield
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane for 24h; Reflux;	15.5 g

2-(2,4,5-trifluorophenyl)acetaldehyde (111991-20-9) → C27H28F3NO2

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 12 h / Reflux 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -20 °C 2.2: 2 h / -20 °C View Scheme

Upstream product

• 165047-24-5 2,4,5-trifluorobenzaldehyde 
• 209995-38-0 (2,4,5-trifluorophenyl)acetic acid 
• 883267-70-7 2-(2,4,5-trifluorophenyl)ethanol 
• 1036273-20-7 2,4,5-trifluorophenylacetic acid methyl ester 
• 367-34-0 2,4,5-trifluoroaniline 

Downstream Products

• 654671-78-0 sitagliptin phosphate 
• 1380521-88-9 (R,R)-N-benzyl-N-(α-methylbenzyl)-1-(2',4',5'-trifluorophenyl)-4-oxo-4-{3''-(trifluoromethyl)-5'',6''-dihydro-1'',2'',4''-triazolo[4,3-α]pyrazin-7''(8''H)-yl}butan-2-amine 
• 486460-32-6 sitagliptin 
• 1380521-84-5 tert-butyl (E)-4-(2',4',5'-trifluorophenyl)but-2-enoate 
• 1349649-83-7 (R)-2-methyl-N-((R)-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-yl)propane-2-sulfinamide 
• 868071-17-4 3(S)-4-(2,4,5-trifluorophenyl)-3-hydroxybutanoic acid 
• 1253056-05-1 (S)-1-(2,4,5-trifluorophenyl)pent-4-en-2-amine 
• 486460-00-8 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 

Relevant academic research and scientific papers

A method for preparing 2, 4, 5 - trifluorobenzene acetic acid (by machine translation)

The invention discloses a 2, 4, 5 - trifluorobenzene acetic acid. The method includes the steps of: (1) the structure shown as formula A 2, 4, 5 - trifluorobenzene diazonium salt with the structure shown in formula II substituted ethylene to carry out coupling reaction, to obtain the intermediate; and (2) the intermediate through hydrolysis or oxidation of the structure is shown as formula I shown in 2, 4, 5 - trifluorobenzene acetic acid; the intermediate comprises a structure of formula IV or a compound represented by the structure of formula C shown 2, 4, 5 - trifluoro phenylacetaldehydes. (by machine translation)

Stereoselective synthesis of 3,4-di-substituted mercaptolactones via photoredox-catalyzed radical addition of thiophenols

A visible light mediated radical addition of thiophenols on 4-phenylbut-3-enoic acids to give diastereoselective synthesis of 3,4-disubstituted γ-lactones is reported. The reaction precludes the conventional prerequisite of conjugate addition. Furthermore, the lactones were successfully utilized in the synthesis of γ-ketoamides.

A west he row sandbank and its salt synthesis method (by machine translation)

The invention discloses a west he row sandbank and its salt synthesis method, in order to 2, 4, 5 - trifluorobenzene acetic acid as the starting material, through esterification, reduction, oxidation and Witting reaction, to obtain 4 - (2, 4, 5 - trifluorophenyl) - 2 - butene ethyl ester, or passes through the reduction, oxidation and Witting reaction after, to obtain 4 - (2, 4, 5 - trifluorophenyl) - 2 - butene ethyl ester. Then in BuLi or six methyl two silicon and nitrogen under the action of the alkane-sodium, with chiral amine on the hydroamination reaction, framed asymmetric amination product, through ester, condensation, hydrogenated three-step reaction to obtain sitagliptin. The west he of the spit of fland synthesis method of raw materials are cheap and easy to obtain, steps are less, the operation is easy, can be effectively reduced. The method can be the high purity of the sitagliptin, the salt of the phosphoric acid obtained after HPLC purity and sitagliptin ee values are in 99% or more, can be applied to the medical field. (by machine translation)

METHOD FOR PRODUCING ALDEHYDE

PROBLEM TO BE SOLVED: To provide a new method for producing aldehyde capable of evading reduction under low temperature conditions and having higher selectivity. SOLUTION: Provided is a method for producing aldehyde where activated ester is prepared from carboxylic acid such as saturated fatty acid, unsaturated fatty acid, hydroxy acid, aromatic carboxylic acid and amino acid and an activation ester agent such as halogenated carbonic acid aryl, a carbodiimide-based condensation agent, an imidazole-based condensation agent and a triazine-based condensation agent, and the activated ester is reduced, and being a method for producing aldehyde in which an environmental load is reduce, and having high yield and high selectivity. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

A method for synthesizing row sandbank west he

The invention discloses a synthetic method for sitagliptin. The method comprises the following steps that: 2,4,5-trifluorobenzaldehyde is used as a starting raw material and undergoes the Wittig reaction and hydrolysis with hydrochloric acid so as to obtain 2-(2,4,5-trifluorophenyl)acetaldehyde; 2-(2,4,5-trifluorophenyl)acetaldehyde and (R)-(+)-t-butyl sulfenamide are subjected to condensation so as to obtain corresponding acetal; acetal and ethyl bromoacetate undergo the Reformatsky reaction, and then an obtained product undergoes hydrolysis so as to obtain organic acid; the organic acid and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride are subjected to condensation so as to obtain acetal of t-butyl sulfenamide of sitagliptin; and finally methanol hydrochloride is used for deprotection so as to obtain sitagliptin. The invention has the following advantages: yield in each step is high, operation is simple, reagents used in the method are conventional reagents, usage of an expensive chiral catalyst is avoided, and good industrial prospect is obtained.

NOVEL BETA-SULFINAMINO MALONATE DERIVATIVES AND PROCESS FOR PREPARING THE SAME, AND PROCESS FOR PREPARING SITAGLIPTIN USING THE SAME

The present invention relates to beta-sulfinamino malonate derivatives having a high diastereomeric ratio (DR) value manufactured through a stereoselective addition reaction of chiral sulfinyl imine and malonate derivatives, to optically pure Sitagliptin by using the same, and to a method for manufacturing pharmaceutically acceptable salt thereof. According to the present invention, the method is capable of manufacturing novel beta-sulfinamino malonate derivatives which are intermediate in the manufacture of Sitagliptin, with high optical purity and high yields without using a solvent under mild conditions, and ultimately manufacturing optically pure Sitagliptin in an efficient manner by using the same.COPYRIGHT KIPO 2016

Asymmetric synthesis of (-)-(R)-sitagliptin

The asymmetric synthesis of (-)-(R)-sitagliptin was achieved in seven steps from commercially available starting materials using the highly diastereoselective conjugate additions of either lithium (R)-N-benzyl-N- (α-methylbenzyl)amide or lithium (R)-N-benzyl-N-(α-methyl-p- methoxybenzyl)amide to tert-butyl 4-(2′,4′,5′-trifluorophenyl) but-2-enoate to install the correct stereochemistry. Subsequent sequential acid-catalysed hydrolysis of the resultant β-amino esters, HOBt/EDC mediated coupling with the triazolopyrazine fragment, and hydrogenolysis gave (-)-(R)-sitagliptin in 43% and 42% overall yields, respectively.