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

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

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)-1-tert-butyloxycarbonyl-3-hydroxypiperidine

The invention discloses a preparation method of (S)-1-tert-butyloxycarbonyl-3-hydroxypiperidine, and relates to the technical field of biological pharmacy. The preparation method comprises the following steps: 1, preparing 3-hydroxypyridine (2) as a raw material; 2, preparing racemic 3-hydroxypiperidine (3) from 3-hydroxypyridine (2); 3, preparing a derivative (2S, 3S)-N-(4-chlorphenyl)-2, 3-dihydroxy succinamic acid (4) from racemic 3-hydroxypiperidine (3) and D-tartaric acid; 4, carrying out resolution reaction on the derivative (2S, 3S)-N-(4-chlorphenyl)-2, 3-dihydroxy succinamic acid (4) prepared from D-tartaric acid to obtain a (S)-hydroxypiperidine salt (5); and 5, subjecting an obtained mixture to extraction, concentration and crystallization, to prepare a (S)-1-tert-butyloxycarbonyl-3-hydroxypiperidine salt (5). The preparation process has the advantages that the synthesis steps are reduced, the yield is increased, an adopted chiral resolving agent can be recycled, and the preparation process 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.

Method for regulating and controlling catalytic hydrogenation reaction of pyridine derivative with redox potential

The invention discloses a method for regulating and controlling catalytic hydrogenation reactions of a pyridine derivative with redox potential. On the basis of data such as redox potential (ORP) andcatalytic hydrogenation reaction process of the pyridine derivative in different medium systems, a scheme that the catalytic hydrogenation reaction of the pyridine derivative is promoted by improvingpyridine derivative ORP with an acid water solution is proposed. As the catalytic hydrogenation reactions of the pyridine derivative are instructed with ORP data, the testing period is shortened, meanwhile, by adopting the process, the pressure of hydrogenation reactions can be reduced, a piperidine product has the advantages of being high in purity, convenient in aftertreatment, and the like, andthus great instruction significances can be achieved for industrial development of the pyridine derivative.

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.

Preparation method of 3-hydroxypiperidine, preparation method of derivative of 3-hydroxypiperidine, and intermediate of 3-hydroxypiperidine

The invention discloses a preparation method of 3-hydroxypiperidine, a preparation method of a derivative of 3-hydroxypiperidine, and an intermediate of 3-hydroxypiperidine. The preparation method of 3-hydroxypiperidine (I) is characterized in that 5-halo-2-hydroxypentylamine halogen acid salt (III) undergoes a ring closure reaction in water under the action of an inorganic alkali to obtain the 3-hydroxypiperidine (I). The preparation method of N-protected 3-hydroxypiperidine (II) comprises the following steps: 1, 5-halo-2-hydroxypentylamine halogen acid salt (III) undergoes the ring closure reaction in water under the action of the inorganic alkali to obtain the 3-hydroxypiperidine (I); and 2, the 3-hydroxypiperidine (I) and a nitrogen protection reagent undergo an N-acylation reaction in an organic solvent under the action of the inorganic alkali to obtain the N-protected 3-hydroxypiperidine (II). The preparation methods have the advantages of simple operation, no expensive catalysts, low production cost, easily available raw materials, simplicity in operation, high reaction conversion rate, high selectivity, simple process, and suitableness for industrial production.

SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1

The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Preparation method of 3-hydroxy piperidine

The invention discloses a preparation method of 3-hydroxy piperidine. The method comprises: subjecting 3-hydroxy pyridine and rhodium-nickel/carbon bi-metal hydrogenation catalyst to reduction reaction in water or an organic solvent under a hydrogen atmosphere so as to obtain 3-hydroxy piperidine. Compared with the existing synthesis method, the method adds the metal additive nickel to improve the hydrogenation catalytic activity of rhodium carbon, carries out reduction reaction under mild conditions, and reduces the equipment pressure. In addition, the rhodium-nickel/carbon bi-metal catalyst has high activity of reducing 3-hydroxy pyridine, has stable properties, and can achieve a product yield of greater than 90%, thus creating good conditions for large-scale production of 3-hydroxy piperidine.

Synthetic method of (S)-N-Boc-3-hydroxypiperidine

The invention discloses a synthetic method of (S)-N-Boc-3-hydroxypiperidine. The synthetic method comprises: hydrogenating 3-hydroxypyridine to obtain 3-hydroxypiperidine; carrying out heating and refluxing on 3-hydroxypiperidine and a resolving agent namely D-pyroglutamic acid in ethanol solution, and cooling to separate out solids so as to obtain (S)-3-hydroxypiperidine D-pyroglutamate; and adding (S)-3-hydroxypiperidine D-pyroglutamate into di-tert-butyl dicarbonate ester under an alkaline condition, and carrying out refining after reaction to obtain (S)-N-Boc-3-hydroxypiperidine. According to the synthetic method disclosed by the invention, by optimizing a synthetic route of (S)-N-Boc-3-hydroxypiperidine and adopting the low-cost and recyclable resolving agent to reduce the production cost, the yield is improved while ensuring the product purity.

Facile arene hydrogenation under flow conditions catalyzed by rhodium or ruthenium on carbon

An efficient and practical protocol for the flow hydrogenation of aromatic rings was developed. The hydrogenation of a variety of aromatic compounds, such as benzene, furan, and pyridine derivatives, could be completed within only 20 s during a single pass through a catalyst cartridge containing 10 % rhodium on carbon (Rh/C) or 10 % ruthenium on carbon (Ru/C) under neutral conditions. The protocol was successfully applied to a 10 mmol scale reaction. Furthermore, the 10 % Rh/C and 10 % Ru/C did not deteriorate during the entire study.