7516-33-8

Usage

Uses

Used in Pharmaceutical Industry:
4-Piperidinone, 1,2,5-trimethylis used as a building block in the synthesis of various pharmaceuticals. Its unique structure and reactivity make it a valuable component in the development of new drugs and medications.
Used in Agrochemical Industry:
In the agrochemical industry, 4-Piperidinone, 1,2,5-trimethylis utilized in the synthesis of agrochemicals, such as pesticides and herbicides. Its properties contribute to the effectiveness and performance of these products in agricultural applications.
Used in Organic Synthesis:
As a versatile building block, 4-Piperidinone, 1,2,5-trimethylis employed in organic synthesis for the creation of a wide range of chemical compounds. Its reactivity and compatibility with various organic solvents make it a valuable component in the synthesis of complex organic molecules.
Used as a Reagent in Chemical Reactions:
4-Piperidinone, 1,2,5-trimethylserves as a reagent in various chemical reactions, facilitating the formation of desired products and improving the efficiency of these processes. Its unique properties make it a useful tool in the field of chemistry.
Safety Precautions:
It is crucial to handle 4-Piperidinone, 1,2,5-trimethylwith care and follow proper safety precautions, as it can be hazardous if not handled properly. Users should be aware of its potential risks and take necessary measures to ensure a safe working environment.

Synthetic route

5-methoxy-2-methyl-1-hexen-3-one (13058-36-1) + methylamine (74-89-5) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
In methanol; water at 60℃; for 4h;	71.2%

3-[(2-methoxycarbonyl-propyl)-methyl-amino]-butyric acid ethyl ester (897400-05-4) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
Stage #1: 3-[(2-methoxycarbonyl-propyl)-methyl-amino]-butyric acid ethyl ester With ethanol; sodium In xylenes at 20 - 75℃; for 8h; Heating / reflux; Stage #2: With hydrogenchloride In water for 6h; Heating / reflux; Stage #3: With potassium hydroxide In water at 0℃; pH=10;	47%

N-(1,2,5-trimethylpiperidylidene-4)aniline (60585-74-2, 127611-57-8, 127611-58-9, 127611-59-0) + benzylmagnesium chloride (6921-34-2) → 1,2,5-trimethyl-4-piperidone (7516-33-8) + 1-methyl-2r,5c-dimethyl-4t-benzyl-4c-phenylaminopiperidine (129115-34-0) + aniline (62-53-3)

Conditions	Yield
In diethyl ether for 8h; Heating;	A n/a B 46% C n/a

5-ethoxy-2-methyl-1-hexen-3-one (103263-54-3) + methylamine (74-89-5) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
In methanol; water at 60℃; for 4h;	45.5%

phenyllithium (591-51-5) + N-(1,2,5-trimethylpiperidinylidene-4-)-β-hydroxyethylamine (113556-34-6) → 1,2,5-trimethyl-4-piperidone (7516-33-8) + ethanolamine (141-43-5) + 1,2,5-trimethyl-4-phenyl-4-N-(β-hydroxyethyl)aminopiperidine (113556-41-5)

Conditions	Yield
In diethyl ether	A n/a B n/a C 11%

2,5-dimethyl-tetrahydro-pyran-4-one (66109-81-7) + methylamine (74-89-5) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
With water

2,5-dimethylpiperidin-4-one (4558-87-6) + methyl iodide (74-88-4) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
With 1,4-dioxane

2-methyl-hexa-1,5-dien-3-yne (820-54-2) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
With water; butan-1-ol Erwaermen unter Zusatz von Schwefelsaeure und Quecksilber(II)-sulfat und Erwaermen des Reaktionsgemisches mit wss. Methylamin in Aethanol;

(E)-2-methylhexa-1,4-dien-3-one (13058-39-4, 105645-96-3, 105645-99-6) + methylamine (74-89-5) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
With water

1,5-dimethoxy-2-methyl-hexan-3-one (41854-15-3) + methylamine (74-89-5) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
With water

2,5-dimethyl-tetrahydro-pyran-4-one (66109-81-7) + water (7732-18-5) + methylamine (74-89-5) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

3-Methyl-3-buten-2-one (814-78-8) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 82.3 percent / NaI, Et3N / acetonitrile / 1 h / 70 °C 2: 60.6 percent / ZnCl2 / ethyl acetate / 1 h / 40 °C 3: 45.5 percent / methanol; H2O / 4 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: 82.3 percent / NaI, Et3N / acetonitrile / 1 h / 70 °C 2: 68.2 percent / ZnCl2 / ethyl acetate / 1 h / 40 °C 3: 71.2 percent / methanol; H2O / 4 h / 60 °C View Scheme

2-methyl-3-<(trimethylsilyl)oxy>-1,3-butadiene (54781-31-6) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60.6 percent / ZnCl2 / ethyl acetate / 1 h / 40 °C 2: 45.5 percent / methanol; H2O / 4 h / 60 °C View Scheme
Multi-step reaction with 2 steps 1: 68.2 percent / ZnCl2 / ethyl acetate / 1 h / 40 °C 2: 71.2 percent / methanol; H2O / 4 h / 60 °C View Scheme

C13H25NO4 (1252678-29-7) → 1,2,5-trimethyl-4-piperidone (7516-33-8)

Conditions	Yield
Stage #1: C13H25NO4 With sodium In 5,5-dimethyl-1,3-cyclohexadiene; ethanol Dieckmann reaction; Reflux; Stage #2: With hydrogenchloride In water Reflux;

1,2,5-trimethyl-4-piperidone (7516-33-8) + 3-methyl-2-pyrazoline-5-one (108-26-9) + malononitrile (109-77-3) → C15H21N5O

Conditions	Yield
In ethanol at 20℃; for 12h;	94%

1,2,5-trimethyl-4-piperidone (7516-33-8) + acetic acid hydrazide (1068-57-1) → 1,2,5-Trimethyl-4-piperidone acetylhydrazone (102689-09-8)

Conditions	Yield
at 20℃; for 0.25h;	90%

1,2,5-trimethyl-4-piperidone (7516-33-8) + 2-aminoethyl vinyl ether (7336-29-0) → 1,2,5-trimethyl-4-(β-vinyloxyethylimino)piperidine (72310-54-4)

Conditions	Yield
In benzene Heating;	85%

1,2,5-trimethyl-4-piperidone (7516-33-8) + (S)-1-phenyl-ethylamine (2627-86-3) → (-)-1,2,5-trimethyl-4-(1S-phenylethylimino)piperidine

Conditions	Yield
With toluene-4-sulfonic acid In benzene Heating;	85%

1,2,5-trimethyl-4-piperidone (7516-33-8) → 1,2,5-trimethylpiperidine-4-one oxime (113849-83-5, 131485-23-9)

Conditions	Yield
With hydroxylamine hydrochloride; sodium acetate In ethanol for 4h; Heating;	81%

1,2,5-trimethyl-4-piperidone (7516-33-8) + acetonitrile (75-05-8) → N-(4-Acetylamino-1,2,5-trimethyl-piperidin-4-yl)-acetamide

Conditions	Yield
With sulfuric acid at 60℃; for 2h;	81%

1,2,5-trimethyl-4-piperidone (7516-33-8) + benzylamine (100-46-9) → N-(1-methyl-2,5-dimethyl-4-piperidylidene)benzylamine (113556-33-5)

Conditions	Yield
With zinc(II) chloride In toluene Heating; catalytic amount of acetic acid, benzene;	76.5%
In toluene Heating;

1,2,5-trimethyl-4-piperidone (7516-33-8) + aniline (62-53-3) → N-(1,2,5-trimethylpiperidylidene-4)aniline (60585-74-2, 127611-57-8, 127611-58-9, 127611-59-0)

Conditions	Yield
With acetic acid In toluene Heating;	72%
With toluene-4-sulfonic acid In benzene Heating;	71.3%

1,2,5-trimethyl-4-piperidone (7516-33-8) + propan-1-ol-3-amine (156-87-6) → N-(1,2,5-trimethylpiperidylidene-4-)-γ-hydroxypropylamine (113556-47-1)

Conditions	Yield
With zinc(II) chloride In toluene Heating; catalytic amount of acetic acid, benzene;	72%

1,2,5-trimethyl-4-piperidone (7516-33-8) → 1,2,5-trimethyl-4-naphthalen-1-ylethynyl-piperidin-4-ol (40964-05-4)

Conditions	Yield
Stage #1: 1-ethynylnaphthalene With n-butyllithium In tetrahydrofuran; hexanes at 0 - 20℃; for 1.08333h; Stage #2: 1,2,5-trimethyl-4-piperidone In tetrahydrofuran; hexanes at 20℃; for 1h;	67%

1,2,5-trimethyl-4-piperidone (7516-33-8) + diethyldiethynylsilane (18292-19-8) → β-isomer of 4-<(diethylethynylsilyl)ethynyl>-1,2,5-trimethyl-4-piperidinol + γ-isomer of 4-<(diethylethynylsilyl)ethynyl>-1,2,5-trimethyl-4-piperidinol

Conditions	Yield
With ethylmagnesium bromide In diethyl ether at 80 - 90℃; for 2h;	A 17.55% B 52.45%

1,2,5-trimethyl-4-piperidone (7516-33-8) + N-methyl-N-propargylaniline (4282-82-0) → 1,2,5-trimethyl-4-hydroxy-4-<3-(N-methyl-N-phenylamino)-propynyl>piperidine + 1,2,5-trimethyl-4-hydroxy-4-<3-(N-methyl-N-phenylamino)-propynyl>piperidine + 1,2,5-trimethyl-4-hydroxy-4-<3-(N-methyl-N-phenylamino)-propynyl>piperidine

Conditions	Yield
With potassium hydroxide In diethyl ether for 8h; Ambient temperature;	A 8% B 32% C 51%

1,2,5-trimethyl-4-piperidone (7516-33-8) + aniline (62-53-3) → 1,2,5-trimethyl-4-N-phenyliminopiperidine (60585-74-2, 127611-57-8, 127611-58-9, 127611-59-0)

Conditions	Yield
With toluene-4-sulfonic acid In benzene Heating;	50%

1,2,5-trimethyl-4-piperidone (7516-33-8) + 1,2-diamino-benzene (95-54-5) → C14H21N3 (83821-86-7) + N-[1,2,5-Trimethyl-piperidin-(4Z)-ylidene]-benzene-1,2-diamine (83821-90-3)

Conditions	Yield
With toluene-4-sulfonic acid In benzene Heating;	A 5% B 50%

1,2,5-trimethyl-4-piperidone (7516-33-8) + rac-methylbenzylamine (618-36-0) → N-(1-methyl-2,5-dimethyl-4-piperidylidene)-α-phenylethylamine (142917-25-7)

Conditions	Yield
In toluene Heating;	49%

1,2,5-trimethyl-4-piperidone (7516-33-8) + m,p-dichloroaniline (95-76-1) → N-(1,2,5-trimethyl-4-piperidylidene)-3,4-dichloroaniline (136038-82-9)

Conditions	Yield
With acetic acid In toluene for 8h; Heating;	40%

1,2,5-trimethyl-4-piperidone (7516-33-8) + 4-p-dimethylaminophenyl-3-buten-2-one (5432-53-1) → 4a-hydroxy-8-(p-dimethylaminophenyl)-2,3,8a-trimethyldecahydro-6-isoquinolone

Conditions	Yield
Stage #1: 1,2,5-trimethyl-4-piperidone With sodium hydride In water; N,N-dimethyl-formamide at 20℃; Mannich reaction; Stage #2: 4-p-dimethylaminophenyl-3-buten-2-one In water; N,N-dimethyl-formamide at 20℃; Mannich reaction;	40%

1,2,5-trimethyl-4-piperidone (7516-33-8) + ethanolamine (141-43-5) → N-(1,2,5-trimethylpiperidinylidene-4-)-β-hydroxyethylamine (113556-34-6)

Conditions	Yield
With zinc(II) chloride In toluene Heating; catalytic amount of acetic acid, benzene;	35%

1,2,5-trimethyl-4-piperidone (7516-33-8) + 1-Phenylbut-1-en-3-one (122-57-6) → 4a-hydroxy-2,3,8a-trimethyl-8-phenyldecahydro-6-isoquinolone

Conditions	Yield
Stage #1: 1,2,5-trimethyl-4-piperidone With sodium hydride In water; N,N-dimethyl-formamide at 20℃; for 1h; Mannich reaction; Stage #2: 1-Phenylbut-1-en-3-one In water; N,N-dimethyl-formamide at 20℃; for 72h; Mannich reaction;	34%

1,2,5-trimethyl-4-piperidone (7516-33-8) + 2,2,6,6-Tetramethyl-4-piperidone (826-36-8) → C20H30N2S

Conditions	Yield
With sulfuric acid at 60 - 65℃; for 4h;	32%

1,2,5-trimethyl-4-piperidone (7516-33-8) + ortho-cresol (95-48-7) → trans-1,2,5-Trimethyl-4-(4-hydroxy-3-methylphenyl)-Δ3-tetrahydropyridine (108332-84-9)

Conditions	Yield
With boron trifluoride diethyl etherate	31%

2-thiazolylamine (96-50-4) + 1,2,5-trimethyl-4-piperidone (7516-33-8) → 1,2,5-trimethyl-4-(2-thiazolyl)iminopiperidine (139117-78-5)

Conditions	Yield
With toluene-4-sulfonic acid In toluene Heating;	30%

1,2,5-trimethyl-4-piperidone (7516-33-8) + 1,3-diphenyl-propen-3-one (614-47-1) → 1,2,5-trimethyl-3-(3-oxo-1,3-diphenylpropyl)piperidin-4-one + 6-hydroxy-1,3,4-trimethyl-6,8-diphenyl-3-azabicyclo[3.3.1]nonan-9-one hydrochloride

Conditions	Yield
With potassium hydroxide In ethanol; water for 5h; Michael reaction;	A 6.39% B 23.2%

1,2,5-trimethyl-4-piperidone (7516-33-8) → 4-(2-methoxy-naphthalen-1-ylethynyl)-1,2,5-trimethyl-piperidin-4-ol

Conditions	Yield
Stage #1: 1-(2',2'-dibromovinyl)-2-methoxynaphthalene With n-butyllithium In tetrahydrofuran; hexanes at -78 - 20℃; for 1.5h; Stage #2: 1,2,5-trimethyl-4-piperidone In tetrahydrofuran; hexanes at 20℃; for 0.25h;	19%

1,2,5-trimethyl-4-piperidone (7516-33-8) + carbon disulfide (75-15-0) + sodium cyanide (143-33-9) → 1,2,5-trimethylpiperidine-4-spiro-5'-imidazolidine-2',4'-dithione

Conditions	Yield
With ammonium chloride In ethanol at 50 - 55℃; for 24h;	18%

1,2,5-trimethyl-4-piperidone (7516-33-8) + (2E)-3-(4-bromophenyl)-1-phenylprop-2-en-1-one (22966-09-2) → 8-(4-bromophenyl)-6-hydroxy-1,3,4-trimethyl-6-phenyl-3-azabicyclo[3.3.1]nonan-9-one hydrochloride

Conditions	Yield
With potassium hydroxide In ethanol; water; benzene for 48h; Michael reaction;	14.6%

Upstream product

• 820-54-2 2-methyl-hexa-1,5-dien-3-yne 
• 13058-39-4 (E)-2-methylhexa-1,4-dien-3-one 
• 74-89-5 methylamine 
• 60585-74-2 N-(1,2,5-trimethylpiperidylidene-4)aniline 
• 6921-34-2 benzylmagnesium chloride 
• 66109-81-7 2,5-dimethyl-tetrahydro-pyran-4-one 
• 7732-18-5 water 
• 93583-33-6 trans-1-α-Phenylethyl-2R,5S-dimethyl-4-piperidone 
• 50-00-0 formaldehyd 
• 4558-87-6 trans-2R,5S-Dimethyl-4-piperidone 
• 93583-33-6 1-α-Phenylethyl-2S,5ξ-dimethyl-4-piperidone 
• 4558-87-6 trans-2S,5R-Dimethyl-4-piperidone 
• 1252678-29-7 C₁₃H₂₅NO₄ 
• 897400-05-4 3-[(2-methoxycarbonyl-propyl)-methyl-amino]-butyric acid ethyl ester 

Downstream Products

• 101255-23-6 1,2,5-trimethyl-4-styryl-piperidin-4-ol 
• 101356-78-9 4-(4-methoxy-phenyl)-1,2,5-trimethyl-piperidin-4-ol 
• 4396-00-3 (+/-)-4-hydroxy-1,2c,5t-trimethyl-piperidine-4r-carbonitrile 
• 110393-39-0 1,2,5-trimethyl-piperidin-4-one-phenylhydrazone; hydrochloride 
• 103396-72-1 1,2,5,1',2',5'-hexamethyl-4,4'-p-phenylene-bis-piperidin-4-ol 
• 95640-01-0 N-(1,2,5-Trimethylpiperidylidene-4)-p-methylaniline 
• 873375-35-0 4-(1-hydroxy-cyclohexylethynyl)-1,2,5-trimethyl-piperidin-4-ol 
• 562-11-8 (+/-)-1,2t,5c-trimethyl-4-phenyl-piperidin-4r-ol 
• 60585-74-2 N-(1,2,5-trimethylpiperidylidene-4)aniline 
• 132982-44-6 o-tolyl-(1,2,5-trimethyl-[4]piperidyliden)-amine 
• 74169-86-1 4-benzyl-1,2,5-trimethyl-piperidin-4-ol 
• 108332-85-0 trans-1,2,5-Trimethyl-4-(4-hydroxy-2-methylphenyl)-Δ³-tetrahydropyridine 
• 108332-84-9 trans-1,2,5-Trimethyl-4-(4-hydroxy-3-methylphenyl)-Δ³-tetrahydropyridine 
• 60585-74-2 1,2,5-trimethyl-4-N-phenyliminopiperidine 

Relevant academic research and scientific papers

Investigation of 4-piperidinols as novel H3 antagonists

Compounds containing a substituted 4-piperidinol core have been found to be potent antagonists of the human H3 receptor. The compounds exhibited up to a 60-fold preference for inhibiting the human H3 receptor over the mouse and showed a low binding affinity for the hERG channel.

4-PIPERIDINOL TERTIARY AMINES AS HISTAMINE 3 RECEPTOR INHIBITORS FOR THE TREATMENT OF OBESITY AND OTHER CNS DISORDERS

This invention relates to compounds having pharmacological activity, to compositions containing these compounds, and to a method of treatment employing the compounds and compositions. More particularly, this invention concerns certain non-imidazole tertiary amine derivatives and their salts and solvates. These compounds have H3 histamine receptor antagonist activity. This invention also relates to pharmaceutical compositions containing these compounds and to a method of treating disorders in which histamine H3 receptor blockade is beneficial.

SYNTHESIS OF 4-SUBSTITUTED 1-METHYL(BENZYL)-2,5-DIMETHYL-4-R-AMINOPIPERIDINES

Schiff base derivatives of 1-methyl(benzyl)-2,5-dimethylpiperidin-4-ones with phenyl, α-pyridyl, benzyl, and β-hydroxyethyl substituents attached to the imine nitrogen atom react with organometallic compounds to give analogously substituted piperidine bases with methyl, allyl, phenyl, and benzyl substituents in the the 4-position.Pure individual geometric isomers of these newly synthetised compound have been isolated and their structures determined.

ASYMMETRIC SYNTHESIS AND ABSOLUTE CONFIGURATION OF 1-α-PHENYLETHYL-2,5-DIMETHYL-4-PIPERIDONE ISOMERS

Reaction of the methyl iodide of trans-1,2-5-trimethyl-4-piperidone with S-α-phenylethylamine proceeds asymmetrically and leads in 66percent optical yield to the formation of the cis- and trans-diastereomeric pair of 1-(α-phenylethyl)-2,5-dimethyl-4-piperidone, in which the new asymmetric centers possess the 2S,5S- and 2S,5R-configurations, respectively.According to x-ray structural analysis, the minor trans-1-(α-phenylethyl)-2,5-dimethyl-4-piperidone component possesses the 2R,5S-configuration.The occurrence of asymmetric synthesis accompanying transamination was confirmed via the preparation of enantiomers of trans-2,5- and trans-1,2,5-trimethyl-4-piperidones.