41661-47-6

Basic information

• Product Name: 4-Piperidinone
• Synonyms: 4-PIPERIDONE;AKOS BBS-00004234;1-((6-chloro-2,3-dihydro-2-(4-methoxyphenyl)-3-oxo-1h-isoindol-1-yl)acetyl)-4-piperidinon;1-yl)acetyl)-;3-dihydro-2-(4-methoxyphenyl)-3-oxo-1h-isoindol-1-yl)acetyl)-1-((6-chloro-;4-Oxopiperidine;4-piperidinone;Piperidin-4-one
• CAS NO: 41661-47-6
• Molecular Formula: C5H9NO
• Molecular Weight: 99.13
• EINECS: 255-481-1
• Product Categories: Miscellaneous
• Mol File: 41661-47-6.mol
• Article Data: 26

Chemical Properties

• Boiling Point: 175.1 °C at 760 mmHg
• Flash Point: 84.6 °C
• Appearance: /
• Density: 1.001 g/cm³
• Vapor Pressure: 1.17mmHg at 25°C
• Refractive Index: 1.448
• PKA: 8.95±0.20(Predicted)
• CAS DataBase Reference: 4-Piperidinone(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Piperidinone(41661-47-6)
• EPA Substance Registry System: 4-Piperidinone(41661-47-6)

Safety Data

• Statements: 11-20/21/22
• Safety Statements: 16-26-36/37/39
• RIDADR: 1993
• HazardClass: IRRITANT
• Hazardous Substances Data: 41661-47-6(Hazardous Substances Data)

Usage

Description

4-Piperidinone is a derivative of piperidine with the molecular formula C5H9NO. 4-Piperidone is used as an intermediate in the manufacture of chemicals and pharmaceutical drugs.Piperidones are a class of chemical compounds sharing the piperidone skeleton. A classic named reaction for the synthesis of piperidones is the Petrenko-Kritschenko piperidone synthesis which involves combining an alkyl-1,3-acetonedicarboxylate with benzaldehyde and an amine. This multicomponent reaction is related to the Hantzsch pyridine synthesis.

InChI:InChI=1/C5H9NO/c7-5-1-3-6-4-2-5/h6H,1-4H2

Synthetic route

N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → piperidin-4-one (41661-47-6)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 3h;	100%
With trifluoroacetic acid In dichloromethane at 20℃;	100%
With trifluoroacetic acid In dichloromethane
With trifluoroacetic acid In 1,2-dichloro-ethane
With hydrogenchloride In 1,4-dioxane at 20℃; for 4h;	6.5 g

benzyl 4-oxo-1-piperidinecarboxylate (19099-93-5) → piperidin-4-one (41661-47-6)

Conditions	Yield
With hydrogen; palladium diacetate; pyrographite In tetrahydrofuran; methanol at 25℃; under 760.051 Torr; for 12h;	99%

4-oxo-piperidine-1-carboxylic acid prop-2-ynyl ester (797751-17-8) → piperidin-4-one (41661-47-6)

Conditions	Yield
With benzyltriethylammonium tetrathiomolybdate In acetonitrile at 20℃; for 2h;	97%

1-((2-nitrophenyl)sulfonyl)piperidin-4-one (267666-09-1) → piperidin-4-one (41661-47-6)

Conditions	Yield
With polystyrene-thiophenol; caesium carbonate; triphenylphosphine In tetrahydrofuran at 20℃; for 24h;	94%

ethene (74-85-1) + methyl 3-aminopropanoate (4138-35-6) → piperidin-4-one (41661-47-6)

Conditions	Yield
Stage #1: ethene; methyl 3-aminopropanoate With sodium ethanolate In ethanol at 5℃; Stage #2: In N,N-dimethyl-formamide at 120℃; for 2h; Concentration; Temperature;	93.7%

N-ethoxycarbonyl-4-piperidone (29976-53-2) → piperidin-4-one (41661-47-6)

Conditions	Yield
With hydrogenchloride In water at 100℃; for 10h;	90.7%

1-phenylmethyl-4-piperidone (3612-20-2) → piperidin-4-one (41661-47-6)

Conditions	Yield
With hydrogen; palladium dihydroxide; palladium on activated charcoal In tetrahydrofuran; water; isopropyl alcohol for 6h;	90%
With palladium on activated charcoal; ammonium formate In methanol for 0.5h; Reflux;	86%
With Pd/C; hydrogen In ethanol

formaldehyd (50-00-0) + acetone (67-64-1) → piperidin-4-one (41661-47-6)

Conditions	Yield
With ammonia at 60 - 70℃; Green chemistry;	68%

4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl-amine (383865-57-4) → piperidin-4-one (41661-47-6) + 4-oxo-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide

Conditions	Yield
	A n/a B 38%

4-methoxy-1,2,3,6-tetrahydro-pyridine → piperidin-4-one (41661-47-6)

Conditions	Yield
With hydrogenchloride

4-phenoxy-1,2,3,6-tetrahydro-pyridine (75571-24-3) → piperidin-4-one (41661-47-6)

Conditions	Yield
With hydrogenchloride

3,3'-imino-di-propionic acid diethyl ester (3518-88-5) → piperidin-4-one (41661-47-6)

Conditions	Yield
With sodium; xylene Erhitzen des entstandenen Piperidon-(4)-carbonsaeure-(3)-aethylesters mit Salzsaeure;
Multi-step reaction with 4 steps 1: potassium carbonate / water / 1.5 h / 0 - 20 °C 2: sodium / ethanol; toluene / 48 h / 20 °C / Inert atmosphere 3: hydrogenchloride / water; ethanol / 7 h / 83 - 85 °C 4: hydrogenchloride / water / 10 h / 100 °C View Scheme

1-acetyl-4-oxo-piperidine-3-carboxylic acid ethyl ester (4451-85-8) → piperidin-4-one (41661-47-6)

Conditions	Yield
With hydrogenchloride; water

ethyl 1-benzoyl-4-oxo-3-piperidinecarboxylate (4451-86-9) → piperidin-4-one (41661-47-6)

C5H9(2)H2NO2 → piperidin-4-one (41661-47-6)

Conditions	Yield
In water-d2 at 34℃; Equilibrium constant;

C8H13(2)H2NO3S → piperidin-4-one (41661-47-6) + 3-mercaptopropanoic acid-d2 (95193-08-1)

Conditions	Yield
With potassium carbonate In water-d2 at 34℃; Equilibrium constant; pH 2.5-3.3;

4-oxy-piperidine → piperidin-4-one (41661-47-6)

Conditions	Yield
With chromium(VI) oxide; acetic acid

di(2-carboxyethyl)amine (505-47-5) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl 2: sodium; xylene / Erhitzen des entstandenen Piperidon-(4)-carbonsaeure-(3)-aethylesters mit Salzsaeure View Scheme

4-Chloropyridine (626-61-9) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: water / 150 °C 2: sodium; alcohol 3: hydrochloric acid View Scheme

4-methoxypyridine (620-08-6) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium; alcohol 2: hydrochloric acid View Scheme

4-phenoxypyridine (4783-86-2) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium; alcohol 2: hydrochloric acid View Scheme

3,3'-benzoylimino-di-propionic acid diethyl ester (101599-56-8) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH; ethanol; benzene View Scheme

3,3'-acetylimino-di-propionic acid diethyl ester (854677-97-7) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium; ethanol; xylene 2: water; hydrochloric acid View Scheme

4-piperidone hydrochloride (41979-39-9) → piperidin-4-one (41661-47-6)

Conditions	Yield
With MP-carbonate resin In dichloromethane at 20℃; for 2h; not specified; Product distribution / selectivity;

ethyl 4-piperidone-3-carboxylate hydrochloride (4644-61-5) → piperidin-4-one (41661-47-6)

Conditions	Yield
With potassium hydroxide

piperidin-4-one hydrochloride monohydrate → piperidin-4-one (41661-47-6)

Conditions	Yield
With magnesium sulfate; sodium hydroxide In dichloromethane

4-HYDROXYPIPERIDINE (5382-16-1) → piperidin-4-one (41661-47-6)

Conditions	Yield
With oxygen In acetonitrile at 70℃; for 2.5h; Catalytic behavior; chemoselective reaction;	75 %Chromat.

Ethyl N-ethoxycarbonyl-3-(2-ethoxycarbonylethylamino)-propionate (83783-66-8) → piperidin-4-one (41661-47-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium / ethanol; toluene / 48 h / 20 °C / Inert atmosphere 2: hydrogenchloride / water; ethanol / 7 h / 83 - 85 °C 3: hydrogenchloride / water / 10 h / 100 °C View Scheme

piperidin-4-one (41661-47-6) + 2-(1H-pyrrol-1-yl)aniline (6025-60-1) → 5'H-spiro[piperidine-4,4'-pyrrolo[1,2-a]quinoxaline] (59474-46-3)

Conditions	Yield
With maleic acid In ethanol for 1h; Heating;	100%

piperidin-4-one (41661-47-6) + 4-methoxy-phenyl-sulphonyl chloride (98-68-0) → 1-(4-methoxybenzenesulfonyl)-4-piperidone (196085-08-2)

Conditions	Yield
With pyridine at 20℃; for 18h;	100%

piperidin-4-one (41661-47-6) + methyl iodide (74-88-4) → N-methyl-4-piperidone hydroiodide (142742-59-4)

Conditions	Yield
In acetone Ambient temperature;	98%

piperidin-4-one (41661-47-6) + vanillin (121-33-5) → (3E,5E)-3,5-bis-(4-hydroxy-3-methoxybenzylidene)piperidin-4-one hydrochloride

Conditions	Yield
With hydrogenchloride; acetic acid at 25 - 30℃; for 2h;	98%
With hydrogenchloride In acetic acid at 25 - 30℃; for 2h;	98%

piperidin-4-one (41661-47-6) + 3,5-di-t-butyl-4-hydroxybenzaldehyde (1620-98-0) → 3,5-bis(3,5-di-tert-butyl-4-hydroxybenz-(E)-ylidene)-4-piperidone hydrochloride

Conditions	Yield
With hydrogenchloride; acetic acid at 25 - 30℃; for 2h;	98%
With hydrogenchloride In acetic acid at 25 - 30℃; for 2h;	98%

piperidin-4-one (41661-47-6) + methyl 6-bromohexanoate (14273-90-6) → C12H21NO3

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 36h; Inert atmosphere;	98%
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 36h; Inert atmosphere;

piperidin-4-one (41661-47-6) + 2-iodo-propane (75-30-9) → 1-Isopropyl-4-piperidone (5355-68-0)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 40℃; for 8h; Temperature; Reagent/catalyst;	97.2%

piperidin-4-one (41661-47-6) + benzyl chloroformate (501-53-1) → benzyl 4-oxo-1-piperidinecarboxylate (19099-93-5)

Conditions	Yield
Stage #1: piperidin-4-one With sodium hydroxide In water; toluene at 0℃; Cooling; Stage #2: benzyl chloroformate In water; toluene at 20℃; for 2h;	97%
With triethylamine In dichloromethane for 0.5h; Ambient temperature;

piperidin-4-one (41661-47-6) + 4-methyl-benzaldehyde (104-87-0) → (3E,5E)-3,5-bis(4-methylbenzylidene)piperidin-4-one (1009817-60-0)

Conditions	Yield
With lithium perchlorate; diethylamine at 20℃;	96%

piperidin-4-one (41661-47-6) + 4-methoxy-benzaldehyde (123-11-5) → (3E,5E)-3,5-bis(4′-methoxybenzylidene)-piperidin-4-one (919091-64-8)

Conditions	Yield
With lithium perchlorate; diethylamine at 20℃;	96%
With sodium hydroxide In ethanol; water at 5 - 8℃; Aldol Condensation;	11.1%

piperidin-4-one (41661-47-6) + epichlorohydrin (106-89-8) → C8H13NO2 (1310417-72-1) + 1-(3-chloro-2-hydroxypropyl)piperidin-4-one (1425504-48-8)

Conditions	Yield
In water at 20℃; for 1h; Solvent;	A 13% B 96%

piperidin-4-one (41661-47-6) + tert-butyl (3-cyano-4,6-dimethylpyridin-2-yl) carbonate → N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3)

Conditions	Yield
In ethanol for 1h; Reflux;	96%

piperidin-4-one (41661-47-6) + di-tert-butyl dicarbonate (24424-99-5) → N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3)

Conditions	Yield
With triethylamine In methanol; dichloromethane at 0 - 25℃; for 12h; Inert atmosphere;	95%
With triethylamine In dichloromethane at 20℃; for 16h;	86%
With sodium hydroxide In tetrahydrofuran for 2h; Ambient temperature;

piperidin-4-one (41661-47-6) + 4-hydrazinobenzene-1-sulfonamide hydrochloride (17852-52-7, 27918-19-0) → 4-piperidinone 4-sulfamoylphenylhydrazone

Conditions	Yield
With hydrogenchloride In ethanol for 3h; Heating;	95%

piperidin-4-one (41661-47-6) + 4-(methylsulfonyl)phenylhydrazine hydrochloride (17852-67-4) → 4-piperidinone 4-methanesulfonylphenylhydrazone monohydrochloride

Conditions	Yield
In ethanol for 2h; Heating;	95%

piperidin-4-one (41661-47-6) + benzaldehyde (100-52-7) → 3,5-dibenzylidenepiperidin-4-one (132766-61-1, 145888-81-9)

Conditions	Yield
With lithium perchlorate; diethylamine at 20℃;	95%
With potassium hydroxide In water at 20℃; for 24h; Aldol Condensation;

piperidin-4-one (41661-47-6) + 3-oxo-3-pyrrolidin-1-yl-propionitrile (14227-95-3) → (2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)pyrrolidin-1-ylmethanone (1099600-09-5)

Conditions	Yield
With sulfur; diethylamine In ethanol at 20℃;	95%

piperidin-4-one (41661-47-6) + chloroform (67-66-3) → 1-formyl-4-piperidone (383193-66-6)

Conditions	Yield
With sodium ethanolate at 50℃; Riemer-Tiemann reaction; Inert atmosphere;	95%

piperidin-4-one (41661-47-6) + 2-Trifluoromethylbenzaldehyde (447-61-0) → N-3,5-bis-(2-(trifluoromethyl)benzylidene)piperidin-4-one

Conditions	Yield
With sodium hydroxide In ethanol at 8℃; for 12h;	95%
In ethanol

piperidin-4-one (41661-47-6) + 6-chloro-2-methylpyridine-3-carboxylic acid (137129-98-7) → 1-(6-chloro-2-methylpyridine-3-carbonyl)piperidin-4-one

Conditions	Yield
With N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridine-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	95%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 4h; Inert atmosphere;	81%

piperidin-4-one (41661-47-6) + propynoic acid methyl ester (922-67-8) + diphenyldisulfane (882-33-7) → C15H17NO3S

Conditions	Yield
With iodine; potassium carbonate In acetonitrile at 60℃; for 4h; regioselective reaction;	95%

piperidin-4-one (41661-47-6) + 4-chlorobenzaldehyde (104-88-1) → (3E,5E)-3,5-bis(4-chlorobenzylidene)-4-piperidone (919091-60-4)

Conditions	Yield
With lithium perchlorate; diethylamine at 20℃;	94%
With potassium hydroxide In water at 20℃; for 24h; Aldol Condensation;

piperidin-4-one (41661-47-6) + ethyl 2-cyanoacetate (105-56-6) → ethyl 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate (24237-44-3)

Conditions	Yield
With sulfur; triethylamine In water at 20℃; for 2h; Gewald Aminoheterocycles Synthesis;	94%
With morpholine; sulfur In ethanol at 50℃;
With morpholine; sulfur In ethanol for 6h; Gewald reaction; Inert atmosphere; Reflux;
With morpholine; octasulfur In ethanol at 20℃; for 24h;
With sulfur; triethylamine In ethanol for 12h; Gewald Aminoheterocycles Synthesis; Reflux;

piperidin-4-one (41661-47-6) + 2-(6-(3-(difluoromethoxy)-5-fluorophenyl)-1-((3-(trifluoromethyl)phenyl)sulfonyl)indolin-2-yl)acetic acid → 1-(2-(6-(3-(difluoromethoxy)-5-fluorophenyl)-1-((3-(trifluoromethyl)phenyl)sulfonyl)indolin-2-yl)acetyl)piperidin-4-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 30℃;	94%

Upstream product

• 3518-88-5 3,3'-imino-di-propionic acid diethyl ester 
• 267666-09-1 1-((2-nitrophenyl)sulfonyl)piperidin-4-one 
• 41979-39-9 4-piperidone hydrochloride 
• 50-00-0 formaldehyd 
• 67-64-1 acetone 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 76-05-1 trifluoroacetic acid 
• 74-85-1 ethene 
• 4138-35-6 methyl 3-aminopropanoate 
• 110-89-4 piperidine 
• 53601-94-8 4-oxo-piperidine-1,3-dicarboxylic acid diethyl ester 
• 83783-66-8 Ethyl N-ethoxycarbonyl-3-(2-ethoxycarbonylethylamino)-propionate 
• 29976-53-2 N-ethoxycarbonyl-4-piperidone 
• 5382-16-1 4-HYDROXYPIPERIDINE 

Downstream Products

• 141945-70-2 1-(4-nitrobenzyl)-4-piperidone 
• 32161-06-1 1-acetyl-4-piperidinone 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 617714-65-5 1-(3,4-dimethyl-benzyl)-piperidin-4-one 
• 220772-52-1 1-(3,4-dichlorobenzyl)-4-piperidone 
• 54635-62-0 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole 
• 66611-26-5 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole 
• 41266-63-1 8-fluoro-2,3,4,5-tetrahydro-1H-pyrido<4,3-b>indole hydrochloride 
• 948853-53-0 1-(2,6-difluorobenzoyl)piperidin-4-one 

Relevant articles and documents

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TEAD INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

Synthesis method of intermediate 4-piperidone

The invention discloses a synthesis method of an intermediate 4-piperidone. The method comprises the following steps: adding beta-alanine methyl ester into ethanol, placing the raw material into a reaction kettle, adding ethylene, uniformly mixing the raw materials, cooling the raw materials to 0-10 DEG C, adding a catalyst aid and sodium ethoxide, stirring the raw materials for reaction, and cooling a reaction product to room temperature after the reaction is finished; and performing reduced pressure distillation to remove ethanol; adding DMF into a reaction kettle, uniformly stirring and mixing the components, heating the mixture to 110-130 DEG C, and carrying out reflux reaction under a stirring condition for 1-2 hours; cooling the reaction product to room temperature, extracting the reaction product with ethyl acetate, performing evaporation to remove ethyl acetate, and carrying out reduced pressure distillation to obtain the 4-piperidone. The synthesis method disclosed by the invention adopts a one-pot method, does not need an intermediate purification step, reduces resource waste, is simple to operate, short in production process, high in raw material conversion rate and relatively low in production cost, and has relatively high economic benefits.