6859-99-0

Basic information

• Product Name: 3-Hydroxypiperidine
• Synonyms: PIPERIDIN-3-OL;3-Hydroxypiperadine;3-PIPERIDINOL;3-HYDROXYPIPERIDINE;3-HYDROXYPIPERIDINE 98%;3-Hydroxypiperidine/3-Piperidinol;3-Hydroxypiperidine, 98% 10GR;3-Hydroxypiperidine, 98% 50GR
• CAS NO: 6859-99-0
• Molecular Formula: C₅H₁₁NO
• Molecular Weight: 101.15
• EINECS: 229-957-4
• Product Categories: FINE Chemical & INTERMEDIATES;Alcohols and Derivatives;Pyrans, Piperidines &Piperazines;Piperidine;Pyrans, Piperidines & Piperazines
• Mol File: 6859-99-0.mol
• Article Data: 15

Chemical Properties

• Melting Point: 56-60 °C
• Boiling Point: 67-69 °C (2 mmHg)
• Flash Point: >100°C
• Appearance: White to light yellow/Crystalline Powder and Lumps
• Density: 1.017 g/cm³
• Vapor Pressure: 0.134mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: ethanol: 0.1 g/mL, clear
• PKA: 14.91±0.20(Predicted)
• Water Solubility: soluble
• Sensitive: Air Sensitive & Hygroscopic
• BRN: 102696
• CAS DataBase Reference: 3-Hydroxypiperidine(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Hydroxypiperidine(6859-99-0)
• EPA Substance Registry System: 3-Hydroxypiperidine(6859-99-0)

Safety Data

• Hazard Codes: C,Xi
• Statements: 34-20/21/22-36/37/38
• Safety Statements: 26-36/37/39-45-27
• RIDADR: UN 3263 8/PG 2
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 6859-99-0(Hazardous Substances Data)

Usage

Description

3-Hydroxypiperidine is a heterocyclic organic compound with the chemical formula C5H9NO2. It features a piperidine ring structure with a hydroxyl group attached to the third carbon atom. 3-Hydroxypiperidine is a versatile intermediate in organic synthesis and has various applications in the pharmaceutical and chemical industries.

Uses

Used in Pharmaceutical Industry:
3-Hydroxypiperidine is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its presence in the molecule allows for the formation of diverse chemical structures with potential therapeutic properties.
Used in Organic Synthesis:
3-Hydroxypiperidine is used as a building block for the synthesis of unsymmetrical ureas, which are important in the development of agrochemicals and pharmaceuticals. The hydroxyl group can be converted into an isocyanate group, facilitating the formation of urea linkages.
Used in Nucleoside Analog Synthesis:
3-Hydroxypiperidine serves as a starting material for the synthesis of piperidine nucleoside analogs. These analogs are of interest in medicinal chemistry due to their potential antiviral and anticancer properties.
Used in Fluorination Reactions:
3-Hydroxypiperidine can be employed in fluorination reactions to introduce fluorine atoms into the molecule. Fluorinated compounds often exhibit improved pharmacokinetic properties, making them valuable in drug development.
Used in Heterocyclic Chemistry:
3-Hydroxypiperidine is used in the synthesis of substituted pyridines, which are important in various chemical and pharmaceutical applications. The presence of the hydroxyl group allows for further functionalization and diversification of the pyridine core.
Used in Specialty Chemicals:
3-Hydroxypiperidine is used as a precursor for the synthesis of 2-pyrrolidinone via oxidation with iodosylbenzene. 3-Hydroxypiperidine is an important solvent and intermediate in the production of various chemicals.
Used in Advanced Synthesis:
3-Hydroxypiperidine may be used to synthesize 1-[2,8-bis(trifluoromethyl)quinolin-4-yl]piperidin-3-ol through a reaction with 4-bromoquinoline. This complex molecule could have potential applications in various fields, such as materials science or medicinal chemistry.

InChI:InChI=1/C5H11NO/c7-5-2-1-3-6-4-5/h5-7H,1-4H2/p+1/t5-/m1/s1

Synthetic route

3-HYDROXYPYRIDINE → 3-hydroxypiperazine (6859-99-0)

1-benzyl-3-hydroxypiperidine (14813-01-5) → 3-hydroxypiperazine (6859-99-0)

Conditions	Yield
With hydrogen; palladium on carbon In tetrahydrofuran; methanol under 2585.81 Torr; for 16h;	98%

5-chloro-2-hydroxypentylamine hydrochloride → 3-hydroxypiperazine (6859-99-0)

Conditions	Yield
With sodium hydroxide In water at 10 - 50℃; for 7h;	85%

5-bromo-2-hydroxypentylamine hydrobromide → 3-hydroxypiperazine (6859-99-0)

Conditions	Yield
With sodium carbonate In water at 10 - 40℃; for 5h;	80%

1-trimethylsilanyl-1,2,3,6-tetrahydro-pyridine (6612-51-7) → 3-hydroxypiperazine (6859-99-0) + 4-HYDROXYPIPERIDINE (5382-16-1)

Conditions	Yield
	A 75% B 25%

3-hydroxypyridine hydrochloride (65520-06-1) → 3-hydroxypiperazine (6859-99-0)

Conditions	Yield
With ethanol; platinum Hydrogenation;

3-hydroxypiperazine (6859-99-0) + benzyl bromide (100-39-0) → 1-benzyl-3-hydroxypiperidine (14813-01-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃;	96%
With caesium carbonate In acetone; toluene at 20℃; for 24h;	88%
In methanol for 2h; Heating;
With potassium carbonate; triethylamine In tetrahydrofuran; hexane; ethyl acetate
Multi-step reaction with 2 steps 1.1: potassium carbonate / toluene / 5 h / 40 - 50 °C 1.2: 2 h / 70 - 80 °C / Inert atmosphere 2.1: ethanol / tert-butyl methyl ether / 3 h / 10 - 20 °C View Scheme

3-hydroxypiperazine (6859-99-0) + di-tert-butyl dicarbonate (24424-99-5) → N-tert-butoxycarbonyl-3-piperidinol (85275-45-2)

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	100%
With triethylamine In methanol at 20℃; for 15h;	99%
With triethylamine In methanol at 20℃; for 15h;	99%

3-hydroxypiperazine (6859-99-0) + tert-butyldicarbonate (34619-03-9) → N-tert-butoxycarbonyl-3-piperidinol (85275-45-2)

Conditions	Yield
In dichloromethane at 20℃; for 15h;	87%
With triethylamine In dichloromethane at 20℃; for 1h;	83.6%
With triethylamine In tetrahydrofuran; dichloromethane	12.66 g (87%)

3-hydroxypiperazine (6859-99-0) + propargyl bromide (106-96-7) → 1-(prop-2-yn-1-yl)piperidin-3-ol

Conditions	Yield
With caesium carbonate In acetone; toluene at 20℃; for 24h; Darkness;	86%
With potassium carbonate In tetrahydrofuran for 6h; Reflux;	67%

3-hydroxypiperazine (6859-99-0) + 4-Fluoronitrobenzene (350-46-9) → 1-(4-nitrophenyl)piperidin-3-ol (99841-68-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 6h;	98%
With potassium carbonate In N-methyl-acetamide	71%

3-hydroxypiperazine (6859-99-0) + 2,4-Dinitrofluorobenzene (70-34-8) → 1-(2,4-dinitrophenyl)piperidine-3-ol (1012966-07-2)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 20℃; for 6h;	91%
With potassium carbonate In dimethyl sulfoxide at 20℃; for 24h;	86%

3-hydroxypiperazine (6859-99-0) + benzenesulfonyl chloride (98-09-9) → 1-(phenylsulfonyl)piperidin-3-ol (1021372-74-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h; Inert atmosphere;	99%
With triethylamine In dichloromethane

3-hydroxypiperazine (6859-99-0) + 4-Fluorobenzoic acid (456-22-4) → (4-fluoro-phenyl)-(3-hydroxy-piperidin-1-yl)-methanone (851883-00-6)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; benzotriazol-1-ol In dichloromethane at 20℃;	53%

3-hydroxypiperazine (6859-99-0) + 6-chloro-N2-(3-chloro-4-methoxy-phenyl)-N4-cycloheptyl-[1,3,5]triazine-2,4-diamine (502767-50-2) → 1-[4-(3-chloro-4-methoxy-phenylamino)-6-cycloheptylamino-[1,3,5]triazine-2-yl]-piperidin-3-ol (676360-88-6)

Conditions	Yield
With sodium hydroxide In benzene	21%
Stage #1: 3-hydroxypiperazine With sodium hydroxide In benzene for 2h; Heating / reflux; Stage #2: 6-chloro-N2-(3-chloro-4-methoxy-phenyl)-N4-cycloheptyl-[1,3,5]triazine-2,4-diamine In benzene at 25℃; for 6h; Heating / reflux;	21%
Stage #1: 3-hydroxypiperazine With sodium hydroxide In benzene for 2h; Heating / reflux; Stage #2: 6-chloro-N2-(3-chloro-4-methoxy-phenyl)-N4-cycloheptyl-[1,3,5]triazine-2,4-diamine In benzene at 25℃; for 6h; Heating / reflux;	21%
Stage #1: 3-hydroxypiperazine With sodium hydroxide In benzene for 2h; Heating / reflux; Stage #2: 6-chloro-N2-(3-chloro-4-methoxy-phenyl)-N4-cycloheptyl-[1,3,5]triazine-2,4-diamine In benzene at 25℃; for 6h; Heating / reflux;	21%
Stage #1: 3-hydroxypiperazine With sodium hydroxide In benzene for 2h; Heating / reflux; Stage #2: 6-chloro-N2-(3-chloro-4-methoxy-phenyl)-N4-cycloheptyl-[1,3,5]triazine-2,4-diamine In benzene at 25℃; for 6h; Heating / reflux;	21%

3-hydroxypiperazine (6859-99-0) + cyclohexylcarbamic acid 2,2,2-trifluoroethyl ester → 3-hydroxypiperidine-1-carboxylic acid cyclohexylamide (606131-61-7)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 100℃; for 4h;	75%

3-hydroxypiperazine (6859-99-0) + (S)-5-chloro-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (1401462-29-0) → 1-(7-(3-((S)-2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ol hydrochloride

Conditions	Yield
Stage #1: 3-hydroxypiperazine; (S)-5-chloro-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine With caesium carbonate; XPhos; tris-(dibenzylideneacetone)dipalladium(0) In 1,4-dioxane at 100℃; for 16h; Inert atmosphere; Stage #2: With hydrogenchloride In water for 0.166667h;	51.8%

3-hydroxypiperazine (6859-99-0) + dichloro(1,5-cyclooctadiene)palladium(II) (12107-56-1) + chloro-diphenylphosphine (1079-66-9) → C30H31Cl2NOP2Pd

Conditions	Yield
Stage #1: 3-hydroxypiperazine; chloro-diphenylphosphine With triethylamine In toluene at -78 - 20℃; for 2.5h; Schlenk technique; Inert atmosphere; Stage #2: dichloro(1,5-cyclooctadiene)palladium(II) In toluene for 4h; Reflux; Schlenk technique; Inert atmosphere;	88%

3-hydroxypiperazine (6859-99-0) + dichloro( 1,5-cyclooctadiene)platinum(ll) (12080-32-9) + chloro-diphenylphosphine (1079-66-9) → C30H31Cl2NOP2Pt

Conditions	Yield
Stage #1: 3-hydroxypiperazine; chloro-diphenylphosphine With triethylamine In toluene at -78 - 20℃; for 2.5h; Schlenk technique; Inert atmosphere; Stage #2: dichloro( 1,5-cyclooctadiene)platinum(ll) In toluene for 4h; Reflux; Schlenk technique; Inert atmosphere;	87%

3-hydroxypiperazine (6859-99-0) + 4-(5-chloro-6-nitrothiazolo[4,5-b]pyridin-2-yl)morpholine → 1-(2-morpholino-6-nitrothiazolo[4,5-b]pyridin-5-yl)piperidin-3-ol

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h;	83.33%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h;	83.33%

(5-Bromo-2-methylpentane-2-sulfonyl)benzene (794533-95-2) + 3-hydroxypiperazine (6859-99-0) → 1-(4-benzenesulfonyl-4-methylpentyl)-3-hydroxypiperidine (794533-72-5)

Conditions	Yield
With potassium carbonate In acetonitrile at 50℃; for 18h;	98%

3-hydroxypiperazine (6859-99-0) + ethyl trifluoroacetate, (383-63-1) → N-trifluoroacetyl-3-hydroxypiperidine (73193-62-1)

Conditions	Yield
With triethylamine In ethanol at 20℃; for 8h;	85%

3-hydroxypiperazine (6859-99-0) + 5-chloro-2-nitroaniline (1635-61-6) → 5-(3'-hydroxypiperidin-1'-yl)-2-nitroaniline

Conditions	Yield
With potassium carbonate In ISOPROPYLAMIDE at 120 - 130℃; for 21h; Inert atmosphere;	86%

3-hydroxypiperazine (6859-99-0) + 2-chloro-5-(trifluoromethyl)-pyrazine (799557-87-2) → 1-(5-(trifluoromethyl)pyrazin-2-yl)piperidin-3-ol (1420466-40-5)

Conditions	Yield
With copper(l) iodide; potassium carbonate; L-proline In dimethyl sulfoxide at 65℃; for 48h; Sealed tube;	94%

3-hydroxypiperazine (6859-99-0) + N-(3-bromopropyl)-4-nitro-1H-pyrazole (1152518-79-0) → 1-(3-(4-nitro-1H-pyrazol-1-yl)propyl)piperidin-3-ol (1422982-43-1)

Conditions	Yield
With caesium carbonate In water; N,N-dimethyl-formamide at 20℃; for 12h;	95%

3-hydroxypiperazine (6859-99-0) + tert-butyl 4-{[4-amino-6-formyl-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f]-[1,2,4]triazin-7-yl]methyl}piperazine-1-carboxylate (1443531-81-4) → rac-1-{[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]methyl}piperidin-3-ol trihydrochloride

Conditions	Yield
Stage #1: 3-hydroxypiperazine; tert-butyl 4-{[4-amino-6-formyl-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f]-[1,2,4]triazin-7-yl]methyl}piperazine-1-carboxylate With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran at 60℃; for 2h; Stage #2: With hydrogenchloride In 1,4-dioxane at 20℃;	100%

3-hydroxypiperazine (6859-99-0) + 4-((4-(4-(trifluoromethoxy)phenyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoic acid → (3-hydroxypiperidin-1-yl)(4-((4-(6-(trifluoromethoxy)pyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)methanone

Conditions	Yield
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 N,N-dimethyl-formamide at 20℃; Inert atmosphere;	89%

3-hydroxypiperazine (6859-99-0) + benzenesufonyl hydrazide (80-17-1) → 1-(phenylsulfonyl)piperidin-3-ol (1021372-74-6)

Conditions	Yield
With tert.-butylhydroperoxide; iodine In water at 20℃; for 0.0166667h;	95%

3-hydroxypiperazine (6859-99-0) + p-bromophenylsulfonyl hydrazide (2297-64-5) → 1-(4-bromophenylsulfonyl)piperidin-3-ol

Conditions	Yield
With tert.-butylhydroperoxide; iodine In water at 20℃; for 0.0166667h;	92%

3-hydroxypiperazine (6859-99-0) + 2-nitrobenzenesulfonyl hydrazide (5906-99-0) → 1-(2-nitrophenylsulfonyl)piperidin-3-ol (1023119-86-9)

Conditions	Yield
With tert.-butylhydroperoxide; iodine In water at 20℃; for 0.0166667h;	92%

3-hydroxypiperazine (6859-99-0) + toluene-4-sulfonic acid hydrazide (1576-35-8) → 1-(p-toluenesulfonyl)-piperidin-3-ol (220384-68-9)

Conditions	Yield
With tert.-butylhydroperoxide; iodine In water at 20℃; for 0.0166667h;	96%

3-hydroxypiperazine (6859-99-0) + acryloyl chloride (814-68-6) → 1-(3-hydroxypiperidin-1-yl)-2-propen-1-one

Conditions	Yield
With triethylamine In dichloromethane at -10℃; for 2h;	85.1%

Upstream product

• 109-00-2 3-HYDROXYPYRIDINE 
• 65520-06-1 3-hydroxypyridine hydrochloride 
• 6612-51-7 1-trimethylsilanyl-1,2,3,6-tetrahydro-pyridine 
• 14813-01-5 1-benzyl-3-hydroxypiperidine 
• 85275-45-2 N-tert-butoxycarbonyl-3-piperidinol 
• 98977-36-7 3-oxo-piperidine-1-carboxylic acid tert-butyl ester 
• 4795-29-3 TETRAHYDROFURFURYLAMINE 
• 636-73-7 3-pyridinesulfonic acid 
• 110-86-1 pyridine 
• 94157-97-8 1?amino?5?chloro?2?pentanol 
• 19141-74-3 5?chloro?1,2?epoxypentane 
• 89280-57-9 1,5?dichloro?2?pentanol 

Downstream Products

• 55578-70-6 1-[2-hydroxy-2-(5-phenyl-isoxazol-3-yl)-ethyl]-piperidin-3-ol 
• 76263-92-8 3-Hydroxypiperidine-N-carbamoylchloride 
• 137488-11-0 1-(2-Hydroxy-4-trifluoromethyl-benzyl)-piperidin-3-ol 
• 85275-45-2 N-tert-butoxycarbonyl-3-piperidinol 
• 104647-43-0 1-[2-(3-hydroxy-1-piperidinyl)ethyl]-2-methyl-3-(4-methoxybenzoyl)-1H-indole 
• 88737-51-3 1--3-(3-hydroxy-1-piperidyl)-propan-2-ol 
• 14813-01-5 1-benzyl-3-hydroxypiperidine 
• 148729-36-6 1-(4-Methoxy-benzyl)-piperidin-3-ol 
• 139652-46-3 (+/-)-6-[6-(3-hydroxypiperidinyl)hexoxy]-2-phenyl-4H-1-benzopyran-4-one 
• 80613-04-3 3-hydroxypiperidine-1-carboxylic acid methyl ester 
• 148729-37-7 1-(2-Methyl-benzyl)-piperidin-3-ol 
• 101767-93-5 1-<(4-methylphenyl)sulfonyl>-3-piperidinol 4-methylbenzenesulfonate ester 
• 99708-28-8 3-(3-hydroxypiperidino)-6-(2-chlorophenyl)pyridazine 
• 3554-62-9 1-isopropyl-3-hydroxypiperidine 

Relevant articles and documents

Multi-chiral nitrogen-substituted piperidinol derivative and preparation method thereof

The invention belongs to the technical field of preparation of chiral piperidine alcohol compounds. The invention particularly relates to a multi-chiral nitrogen-substituted piperidinol derivative and a preparation method thereof. The 3 -hydroxypyridine serves as a starting raw material, and the corresponding substrate is obtained through catalytic hydrogenation reduction, amino protection, hydroxyl oxidation and Stork enamine - carbon alkylation to obtain the corresponding substrate. The process is simple, the reaction conditions are mild, and in particular, the ketone reducing liquid enzyme (KRED - 101) is selectively catalyzed, so that a chiral target product is obtained, and the yield is stable and the three wastes are few. The obtained piperidine heterocyclic derivative with the chiral center body has a plurality of drug activities and is suitable for industrial production.

Preparation method of (S)-N-BOC-3-hydroxypiperidine

The invention provides a preparation method of (S)-N-BOC-3-hydroxypiperidine. The preparation method comprises the following steps: carrying out a reaction on (S)-epichlorohydrin with a 2-chloroethylmagnesium bromide Grignard reagent to obtain (S)-1,5-dichloro-2-pentanol, carrying out an intramolecular cyclization reaction in the presence of an alkaline substance to generate (S)-5-chloro-1,2-epoxypentane, carrying out a reaction on the (S)-5-chloro-1,2-epoxypentane with an ammonia solution to generate (S)-1-amino-5-chloro-2-pentanol, then carrying out an intramolecular cyclization reaction onthe (S)-1-amino-5-chloro-2-pentanol to obtain (S)-3-hydroxypiperidine, and finally carrying out a reaction with BOC anhydride to obtain the product (S)-N-BOC-3-hydroxypiperidine. The preparation method disclosed by the invention has the advantages of short synthesis route, few side reactions and high yield; the product has good quality and is convenient for purification. The raw materials are easily available and has low price; the reaction conditions are mild; and safety is high. The preparation method is environmentally friendly, is simple and practice, and is suitable for industrial batchproduction.

Preparation method of (S)-3-hydroxypiperidine

The invention discloses a preparation method of (S)-3-hydroxypiperidine. The preparation method comprises the steps of (1) carrying out catalytic hydrogenation on 3-hydroxypyridine to prepare 3-hydroxypiperidine; (2) splitting the 3-hydroxypiperidine for preparing the (S)-3-hydroxypiperidine, wherein catalytic hydrogenation is carried out under the co-catalysis of a ruthenium/silicon dioxide catalyst and a cocatalyst; the weight ratio of the ruthenium/silicon dioxide catalyst to the cocatalyst is 1:1 to 3:1; the total weight of the ruthenium/silicon dioxide catalyst and the cocatalyst is 5 to10 percent of the weight of the 3-hydroxypiperidine; and the cocatalyst is aluminum oxide. According to the method provided by the invention, the ruthenium/silicon dioxide catalyst and the aluminum oxide are adopted as a compound catalyst for catalytic hydrogenation, and the compound catalyst is relatively cheap but has the same better catalysis effect, and pollutes environment less so as to be suitable for industrial production.