3433-37-2

Basic information

• Product Name: 2-(Hydroxymethyl)piperidine
• Synonyms: 2-PiperidineMethanol or 2-(HydroxyMethyl)piperidine;2-Piperidinemethanol 97%;piperidin-2-ylmethanol hydrochloride;2-(HYDROXYMETHYL)PIPERIDINE;2-PIPERIDINYLMETHANOL;2-PIPERIDINEMETHANOL;PIPERIDIN-2-YL-METHANOL;2-Piperidine-methanol(2-(Hydroxymethyl)-piperidine)
• CAS NO: 3433-37-2
• Molecular Formula: C₆H₁₃NO
• Molecular Weight: 115.17
• EINECS: 222-333-2
• Product Categories: Piperidines;Piperidine;Alkohols;Heterocyclic Compounds;Building Blocks;C5 to C7;Chemical Synthesis;Heterocyclic Building Blocks
• Mol File: 3433-37-2.mol
• Article Data: 14

Chemical Properties

• Melting Point: 68-70 °C(lit.)
• Boiling Point: 100-102°C (6 mmHg)
• Flash Point: 68-70°C(lit.)
• Appearance: White to pale yellow/Solid
• Density: 0.9837 (rough estimate)
• Vapor Pressure: 0.0225mmHg at 25°C
• Refractive Index: 1.4775 (estimate)
• Storage Temp.: Room temperature.
• Solubility: soluble in Methanol
• PKA: 15.08±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: 2-(Hydroxymethyl)piperidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(Hydroxymethyl)piperidine(3433-37-2)
• EPA Substance Registry System: 2-(Hydroxymethyl)piperidine(3433-37-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: 3263
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 3433-37-2(Hazardous Substances Data)

Usage

Chemical Properties

WHITE TO SLIGHTLY BROWN SOLID

Uses

2-Piperidinemethanol was used in the synthesis of 3-phenyloctahydropyrido[2,1-c][1,4]oxazine hydrochloride and the 10R and 10S diastereomers.

InChI:InChI=1/C6H13NO/c8-5-6-3-1-2-4-7-6/h6-8H,1-5H2/p+1/t6-/m0/s1

Synthetic route

ethyl 6-oxopiperidine-2-carboxylate (127274-92-4) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With lithium aluminium tetrahydride	88%

ethyl-2-picolinate (2524-52-9) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With ethanol; sodium
With ethanol; nickel at 50℃; under 110326 - 147102 Torr; Hydrogenation;

ethyl pipecolate (15862-72-3) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether

N-benzoyl-2-<(benzoyloxy)methyl>piperidine (94685-29-7) → N-benzoyl-2-(hydroxymethyl)piperidine (92041-11-7) + piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; methanol other N,O-diacylated compounds, other reagents;

pipecolic Acid (4043-87-2) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With borane In tetrahydrofuran Ambient temperature;
With lithium aluminium tetrahydride

pyridine-2-carbaldehyde (1121-60-4) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With hydrogenchloride; hydrogen; platinum(IV) oxide In ethanol under 41253.3 Torr; for 16h;	100 % Spectr.

methyl pipecolinate (35677-83-9, 41994-45-0, 43041-11-8, 90710-04-6) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With sodium tetrahydroborate; sodium hydrogencarbonate

tert-butyl 2-(hydroxymethyl)piperidine-1-carboxylate (157634-00-9) → piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; water at 0 - 20℃; for 2h;

2,6-diaminohexanoic acid hydrochloride (70-53-1) → piperidine (110-89-4) + 2-Methylpiperidin (109-05-7, 3000-79-1) + piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid / water / 20 - 30 °C 1.2: 120 °C / 36228.6 Torr / Autoclave; Sealed tube 2.1: 5% active carbon-supported ruthenium / water / 7 h / 150 °C / 67506.8 Torr / pH 3.1 View Scheme

2,6-diamino-1-hexanol (25441-01-4) → piperidine (110-89-4) + 2-Methylpiperidin (109-05-7, 3000-79-1) + piperidin-2-ylmethanol (3433-37-2)

Conditions	Yield
With 5% active carbon-supported ruthenium In water at 150℃; under 67506.8 Torr; for 7h; pH=3.1;

acrylonitrile (107-13-1) + piperidin-2-ylmethanol (3433-37-2) → 3-(2-hydroxymethylpiperidin-1-yl)propionitrile (76393-93-6)

Conditions	Yield
In methanol	100%
at 70 - 80℃; for 1h;

di-tert-butyl dicarbonate (24424-99-5) + piperidin-2-ylmethanol (3433-37-2) → tert-butyl 2-(hydroxymethyl)piperidine-1-carboxylate (157634-00-9)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 16h;	100%
In acetonitrile at 20℃; for 24h;	99%
With triethylamine In dichloromethane for 14h; alkoxycarbonylation;	96%

piperidin-2-ylmethanol (3433-37-2) + 6-benzylsulfanyl-2-iodo-9-(tetrahydropyran-2-yl)-9H-purine (403620-90-6) → {1-[6-benzylsulfanyl-9-(tetrahydropyran-2-yl)-9H-purin-2-yl]-piperidin-2-yl}-methanol (403620-91-7)

Conditions	Yield
With triisopropylamine; 2,4-dichlorophenoxyacetic acid dimethylamine at 110℃; for 4h;	100%
With tri-n-propylamine In N,N-dimethyl acetamide at 120℃;	68%

methanol (67-56-1) + piperidin-2-ylmethanol (3433-37-2) → (1-methyl-piperidin-2-yl)-methanol (20845-34-5)

Conditions	Yield
chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium (II) at 100℃;	100%
With cesiumhydroxide monohydrate; (1,4-dimethyl-5,7-diphenyl-1,2,3,4-tetrahydro-6H-cyclopenta[b]pyrazin-6-one) irontricarbonyl complex3; hydrogen at 110℃; under 7600.51 Torr; Autoclave;	88%

4-methoxy-2,6-dimethylbenzenesulfonyl chloride (55661-08-0) + piperidin-2-ylmethanol (3433-37-2) → [1-(4-methoxy-2,6-dimethyl-phenylsulfonyl)-piperidin-2-yl]-methanol (1021373-55-6)

Conditions	Yield
With potassium carbonate In acetone at 50℃; Product distribution / selectivity;	100%
With triethylamine In dichloromethane at 0 - 20℃;	79%
With triethylamine In dichloromethane at 0 - 20℃;	63%

(R)-1-(3-((3'-(3-bromopropoxy)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)oxy)propyl)pyrrolidin-3-ol + piperidin-2-ylmethanol (3433-37-2) → (3R)-1-(3-((3'-(3-(2-(hydroxymethyl)piperidin-1-yl)propoxy)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)oxy)propyl)pyrrolidin-3-ol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In methanol at 65℃; Inert atmosphere;	100%

p-toluenesulfonyl chloride (98-59-9) + piperidin-2-ylmethanol (3433-37-2) → Toluene-4-sulfonic acid 1-(toluene-4-sulfonyl)-piperidin-2-ylmethyl ester (63587-45-1)

Conditions	Yield
With pyridine at 20℃; for 18h; Cooling with ice;	99.6%
With dmap; triethylamine In dichloromethane Ambient temperature;

1-bromo-4-methylpent-3-ene (2270-59-9) + piperidin-2-ylmethanol (3433-37-2) → (+/-)-<1-(4-methyl-3-pentenyl)-2-piperidyl>methanol (167750-59-6)

Conditions	Yield
With potassium carbonate In toluene at 110℃; for 72h;	99%

benzyl bromide (100-39-0) + piperidin-2-ylmethanol (3433-37-2) → (1-benzylpiperidin-2-yl)methanol (137650-02-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 18 - 25℃; for 2h;	99%
With potassium carbonate In ethanol at 80℃; for 12h;	93%
With potassium carbonate In toluene for 16h; Alkylation; Heating;	81%

tert-butyldimethylsilyl chloride (18162-48-6) + piperidin-2-ylmethanol (3433-37-2) → 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)piperidine (135938-63-5)

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 4h;	99%
With 1H-imidazole In dichloromethane at 20℃; for 4.5h;	99%
With 1H-imidazole In dichloromethane Inert atmosphere;	98%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃;	92%
With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; Product distribution / selectivity;

piperidin-2-ylmethanol (3433-37-2) → (RS)-2-Brommethylpiperidin-hydrobromid (3433-38-3)

Conditions	Yield
With sulfurous dibromide; N,N-dimethyl-formamide In toluene at 50℃; for 8h; Inert atmosphere;	98%
With hydrogen bromide; phosphorus tribromide 1) water;	86%
With hydrogen bromide In water for 24h; Reflux;	76%

(Z)-4-(2'-bromo-3'-chloroprop-1'-enyl)-1,2-dimethoxybenzene (741719-72-2) + piperidin-2-ylmethanol (3433-37-2) → {1-[(Z)-2'-bromo-3'-(3'',4''-dimethoxyphenyl)prop-2'-enyl]piperidin-2-yl}methanol (741719-59-5)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 70℃; for 16h;	98%

methylpolyethyleneglycol-3-acetoxy-2-methylenehexanoate + piperidin-2-ylmethanol (3433-37-2) → methylpolyethyleneglycol-2-(2-hydroxymethylpiperidine-1-ylmethyl)hex-2-enoate

Conditions	Yield
With potassium carbonate In dichloromethane at 20℃; for 6h; Substitution;	97%

PVS (5535-48-8) + piperidin-2-ylmethanol (3433-37-2) → [1-(2-benzenesulfonyl-ethyl)-piperidin-2-yl]-methanol (640296-99-7)

Conditions	Yield
In xylene for 24h; Heating;	96%

2-(bromoacetyl)-10-methyl-phenothiazine (1579944-63-0) + piperidin-2-ylmethanol (3433-37-2) → 3-(10-methyl-2-phenothiazinyl)-octahydro-1,4-pyrido[2,1-c]morpholin-3-ol hydrobromide (1579944-50-5)

Conditions	Yield
Stage #1: 2-(bromoacetyl)-10-methyl-phenothiazine; piperidin-2-ylmethanol In diethyl ether; acetone at 20℃; for 24h; Stage #2: With hydrogen bromide In diethyl ether	96%

phosgene (75-44-5) + piperidin-2-ylmethanol (3433-37-2) → hexahydro-3H-oxazolo<3,4-a>pyridin-3-one (42329-17-9)

Conditions	Yield
With triethylamine In dichloromethane at -60℃;	94%

Methyl 3-acetoxy-2-methylene-3-phenylpropanoate (124957-36-4) + piperidin-2-ylmethanol (3433-37-2) → (Z)-2-(2-Hydroxymethyl-piperidin-1-ylmethyl)-3-phenyl-acrylic acid methyl ester (505030-55-7)

Conditions	Yield
With potassium carbonate In dichloromethane at 20℃; for 10h;	94%

(Z,E,E)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenoic acid (35750-48-2) + piperidin-2-ylmethanol (3433-37-2) → N-(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenoyl)-2-hydroxymethylpiperidine

Conditions	Yield
	94%

benzoyl chloride (98-88-4) + piperidin-2-ylmethanol (3433-37-2) → N-benzoyl-2-(hydroxymethyl)piperidine (92041-11-7) + N-benzoyl-2-<(benzoyloxy)methyl>piperidine (94685-29-7)

Conditions	Yield
With di(n-butyl)tin oxide; triethylamine In toluene for 0.15h; Irradiation;	A 93% B 5%
With di(n-butyl)tin oxide; triethylamine In toluene for 0.15h; Product distribution; Irradiation; other amino alcohols, other acyl chlorides, effect of the power output at the microwave-mediated acylation;	A 81% B 5%
With di(n-butyl)tin oxide; triethylamine In toluene for 0.15h; Irradiation;	A 78% B 14%

ortho-toluoyl chloride (933-88-0) + piperidin-2-ylmethanol (3433-37-2) → 2-(hydroxymethyl)-N-(2-methylbenzoyl)piperidine (115512-60-2) + 2-Methyl-benzoic acid 1-(2-methyl-benzoyl)-piperidin-2-ylmethyl ester

Conditions	Yield
With di(n-butyl)tin oxide; triethylamine In toluene for 0.15h; Irradiation;	A 93% B n/a

carbon disulfide (75-15-0) + piperidin-2-ylmethanol (3433-37-2) → (+/-)-tetrahydro-1H-thiazolo[3,4-a]pyridin-3(5H)-thione

Conditions	Yield
With sodium hydroxide In water at 20℃; for 24h; Inert atmosphere;	93%

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + piperidin-2-ylmethanol (3433-37-2) → C21H23NO3 (170867-95-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	93%

Glyoxal (131543-46-9) + 4-methoxyphenylboronic acid (5720-07-0) + piperidin-2-ylmethanol (3433-37-2) → C15H21NO3

Conditions	Yield
In ethanol; water at 20℃; for 24h;	93%

benzyl chloroformate (501-53-1) + piperidin-2-ylmethanol (3433-37-2) → 1-benzyloxycarbonyl-2-hydroxymethylpiperidine (105706-75-0)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 65℃; for 0.166667h; microwave irradiation;	92%
With potassium carbonate In tetrahydrofuran Ambient temperature;	90%
With potassium carbonate In tetrahydrofuran; water at 0 - 20℃; for 24h;
With triethylamine

methyl chloroformate (79-22-1) + piperidin-2-ylmethanol (3433-37-2) → methyl 2-(hydroxymethyl)-1-piperidinecarboxylate (165104-66-5)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at 0 - 26℃;	92%

phosgene (75-44-5) + piperidin-2-ylmethanol (3433-37-2) → 2-(Hydroxymethyl)piperidine-N-carbamoyl chloride (75431-14-0)

Conditions	Yield
With triethylamine In dichloromethane at -65℃; for 15h;	91%

2-Fluor-5-nitrobenzoesaeure-aethylester (367-79-3) + piperidin-2-ylmethanol (3433-37-2) → 9-Nitro-1,2,3,4,4a,5-hexahydropyrido<1,2-a><4,1>benzoxazepin-7-on (85155-91-5)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; N-ethyl-N,N-diisopropylamine at 50℃; for 18h;	91%

4-methyl-benzoyl chloride (874-60-2) + piperidin-2-ylmethanol (3433-37-2) → (2-Hydroxymethyl-piperidin-1-yl)-p-tolyl-methanone + 4-Methyl-benzoic acid 1-(4-methyl-benzoyl)-piperidin-2-ylmethyl ester

Conditions	Yield
With di(n-butyl)tin oxide; triethylamine In toluene for 0.15h; Irradiation;	A 91% B n/a
With triethylamine In toluene for 0.15h; Irradiation;	A 21% B 11%

2-Chloromethylthiophene (765-50-4) + piperidin-2-ylmethanol (3433-37-2) → 1-(thien-2-ylmethyl)piperidine-2-methanol (130054-59-0)

Conditions	Yield
With potassium carbonate In acetonitrile for 4h; Heating; chloromethyl-thiophene added in two portions;	90%

chloroacetonitrile (107-14-2) + piperidin-2-ylmethanol (3433-37-2) → 2-hydroxymethylpiperidin-1-ylacetonitrile (186790-31-8)

Conditions	Yield
With triethylamine In methanol for 24h; Ambient temperature;	90%

Upstream product

• 25441-01-4 2,6-diamino-1-hexanol 
• 70-53-1 2,6-diaminohexanoic acid hydrochloride 
• 157634-00-9 tert-butyl 2-(hydroxymethyl)piperidine-1-carboxylate 
• 35677-83-9 methyl pipecolinate 
• 1121-60-4 pyridine-2-carbaldehyde 
• 4043-87-2 pipecolic Acid 
• 94685-29-7 N-benzoyl-2-<(benzoyloxy)methyl>piperidine 
• 127274-92-4 ethyl 6-oxopiperidine-2-carboxylate 
• 15862-72-3 ethyl pipecolate 
• 2524-52-9 ethyl-2-picolinate 

Downstream Products

• 6833-37-0 perhydro-oxazolo<3,4-a>pyridine 
• 73332-34-0 1,2,3,4,4a,5-hexahydro-pyrido[1',2':4,5][1,4]oxazino[2,3-b]quinoxaline 
• 62835-04-5 2-phenyl-hexahydro-spiro[cycloheptane-1,3'-oxazolo[3,4-a]pyridine] 
• 14733-59-6 3-benzyl-hexahydro-oxazolo[3,4-a]pyridine 
• 2563-84-0 3-phenylhexahydro-1H-oxazolo[3,4-a]pyridine 
• 38436-63-4 2-Oxa-3-oxo-chinolizidin 
• 38384-83-7 2-Oxa-4-oxo-chinolizidin 
• 95770-77-7 4-phenyl-hexahydro-pyrido[2,1-c][1,4]oxazin-3-one 
• 95770-79-9 3-phenyl-hexahydro-pyrido[2,1-c][1,4]oxazin-4-one 
• 75431-14-0 2-(Hydroxymethyl)piperidine-N-carbamoyl chloride 
• 19028-69-4 (1-acetyl-piperidin-2-yl)-methanol 
• 128103-38-8 1-<(3,4-dichlorophenyl)acetyl>-2-piperidinemethanol 
• 85147-39-3 <2-(2-Hydroxymethyl)piperidino-5-nitrophenyl>phenylmethanon 
• 137059-42-8 N-<2-(phenylsulfonyl)-2-propenyl>-2-piperidinemethanol 

Relevant articles and documents

The synthesis of a new 8-azaprostanoid [1]

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Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds

Novel piperidine and piperazine derivatives have been designed and tested as inhibitors of LTA4 hydrolase (LTA4H). Most potent compounds showed good potency in both enzymatic and functional human whole blood assay. Crystallography studies further confirmed observed structure-activity relationship and LTA4H binding mode for analogs from the piperidine series.

Partial hydrogenation of substituted pyridines and quinolines: A crucial role of the reaction conditions

Hydrogenation of pyridyl and quinolyl compounds 2-substituted with a carbonyl group (1a-c and 2b,c) using PtO2 and 1 equiv. of HCl (conditions A) provides clean and total formation of the desired amino alcohol (hydrogenation of the heterocyclic ring and of the carbonyl) while under conditions B1 and/or B2 (concentrated HCl or pure CF 3CO2H) the heterocyclic ring remains untouched and other aromatic parts are hydrogenated providing complex mixtures. When the heterocyclic ring is substituted by an alkyl group (quinaldine 3) conditions A provide mixtures while under conditions B2 (pure CF 3CO2H) the benzene ring is cleanly hydrogenated leading to a pure product.