111991-20-9

Basic information

• Product Name: 2-(2,4,5-trifluorophenyl)acetaldehyde
• Synonyms: 2-(2,4,5-trifluorophenyl)acetaldehyde;Benzeneacetaldehyde, 2,4,5-trifluoro-;(2,4,5-Trifluorophenyl)acetaldehyde
• CAS NO: 111991-20-9
• Molecular Formula: C₈H₅F₃O
• Molecular Weight: 174.12
• Mol File: 111991-20-9.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 196.8±35.0 °C(Predicted)
• Appearance: /
• Density: 1.317±0.06 g/cm3(Predicted)
• CAS DataBase Reference: 2-(2,4,5-trifluorophenyl)acetaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(2,4,5-trifluorophenyl)acetaldehyde(111991-20-9)
• EPA Substance Registry System: 2-(2,4,5-trifluorophenyl)acetaldehyde(111991-20-9)

Safety Data

• Hazardous Substances Data: 111991-20-9(Hazardous Substances Data)

Usage

Uses

2-(2,4,5-Trifluorophenyl)acetaldehyde is derived from 2,4,5-Trifluorobenzeneacetic Acid (T792625), which 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.

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

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

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 
• 209995-38-0 (2,4,5-trifluorophenyl)acetic acid 
• 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 
• 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 
• 486460-00-8 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 

Relevant articles and documents

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)

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)

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