15862-72-3

Basic information

• Product Name: Ethyl pipecolinate
• Synonyms: 2-Piperidinecarboxylic acid, ethyl ester;LABOTEST-BB LT00233125;DL-HOMOPROLINE ETHYL ESTER;ETHYL 2-PIPERIDINECARBOXYLATE;ETHYL DL-PIPECOLINATE;(+/-)-ETHYL PIPERIDINE-2-CARBOXYLATE;ETHYL PIPECOLINATE;PIPERIDINE-2-CARBOXYLIC ACID ETHYL ESTER
• CAS NO: 15862-72-3
• Molecular Formula: C₈H₁₅NO₂
• Molecular Weight: 157.21
• EINECS: 239-990-6
• Product Categories: Piperidine
• Mol File: 15862-72-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 216-217 °C(lit.)
• Flash Point: 115 °F
• Appearance: Clear colorless to light yellow/Liquid
• Density: 1.014 g/mL at 20 °C(lit.)
• Refractive Index: n20/D 1.456
• Storage Temp.: 2-8°C
• PKA: 8.40±0.10(Predicted)
• BRN: 81694
• CAS DataBase Reference: Ethyl pipecolinate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl pipecolinate(15862-72-3)
• EPA Substance Registry System: Ethyl pipecolinate(15862-72-3)

Safety Data

• Hazard Codes: Xi,C
• Statements: 10-36/37/38-34-20/21
• Safety Statements: 26-36-36/37/39
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• F: 10
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 15862-72-3(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to light yellow liquid

Uses

Reactant for: Combinatorial chemistry with hydrazones Swift hydroamination Synthesis of HCV NS5B polymerase inhibitors Preparation of selective androgen receptor modulators Decarbonylative arylation at sp3 carbon centers Synthesis of quinoline derivatives as selective a2C-adrenoceptor antagonists

Synthetic route

ethyl-2-picolinate (2524-52-9) → ethyl pipecolate (15862-72-3)

Conditions	Yield
With carbamic acid, phenyl-, 1-methylethyl ester; hydrogen; [(norbornadiene)rhodium(I)chloride]2 In tetrahydrofuran at 60℃; under 75006 Torr; for 20h; Product distribution; Further Variations:; Catalysts; Solvents; Reagents;	100%
With 1,4-dioxane; nickel at 150℃; under 183877 Torr; Hydrogenation;

ethanol (64-17-5) + pipecolic Acid (4043-87-2) → ethyl pipecolate (15862-72-3)

Conditions	Yield
With thionyl chloride at 0℃; for 2h; Reflux; Inert atmosphere;	93%
With thionyl chloride for 3h; Heating;
With thionyl chloride In ethanol for 5h; Reflux;

pipecolic Acid (4043-87-2) → ethyl pipecolate (15862-72-3)

Conditions	Yield
With ethanol; sulfuric acid

ethanol (64-17-5) + hydrochloride of/the/ pipecolic acid → ethyl pipecolate (15862-72-3)

Conditions	Yield
With sulfuric acid

2-Picolinic acid (98-98-6) → ethyl pipecolate (15862-72-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium; amyl alcohol 2: ethanol; H2SO4 View Scheme

1-Hydroxymethyl-1H-benzotriazole (28539-02-8) + ethyl pipecolate (15862-72-3) → N-<(benzotriazolyl)methyl>-pipecolinic acid ethyl ester (170164-57-5)

Conditions	Yield
In ethanol for 12h; Ambient temperature;	100%

ethyl pipecolate (15862-72-3) → ethyl N-chloropipecolinate (219718-34-0)

Conditions	Yield
With sodium hypochlorite; acetic acid; tert-butyl alcohol In various solvent(s) at 0℃; for 0.5h;	100%
With N-chloro-succinimide In diethyl ether at 0 - 5℃; for 4h;	85%

3,4-dimethoxy-2-allylbenzaldehyde (92345-90-9) + ethyl pipecolate (15862-72-3) → (5aS,10aR,11aS)-8,9-Dimethoxy-1,2,3,4,5a,10,10a,11-octahydro-indeno[2,1-b]indolizine-11a-carboxylic acid ethyl ester (92345-93-2)

Conditions	Yield
In toluene Heating;	99%

N-(2-Hydroxyethyl)phthalimide (3891-07-4) + ethyl pipecolate (15862-72-3) → 1-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-piperidine-2-carboxylic acid ethyl ester (139579-84-3)

Conditions	Yield
Stage #1: N-(2-Hydroxyethyl)phthalimide With trifluoromethylsulfonic anhydride In dichloromethane at 0℃; for 0.166667h; Stage #2: ethyl pipecolate With 2,6-dimethylpyridine; TEA In dichloromethane at 20℃;	98%

ethyl pipecolate (15862-72-3) + allylmagnesium bromide (1730-25-2) → 4-(piperidine-2-yl)-hepta-1,6-dien-4-ol (937653-56-0)

Conditions	Yield
In diethyl ether at 0℃; Reflux; Inert atmosphere;	98%

ethyl pipecolate (15862-72-3) + (4-bromomethyl)benzaldehyde dimethyl acetal (138498-84-7) → C18H27NO4 (1221440-41-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 18h;	98%

ethyl pipecolate (15862-72-3) + 2-naphthaloyl chloride (2243-83-6) → 1-(Naphthalene-2-carbonyl)-piperidine-2-carboxylic acid ethyl ester (105855-19-4)

Conditions	Yield
With pyridine In toluene Ambient temperature;	96.5%

zinc trifluoromethanesulfonate (54010-75-2) + ethyl pipecolate (15862-72-3) → C18H30F6N2O10S2Zn

Conditions	Yield
In benzene at 80℃; for 1h;	96%

2-chloroethyl isothiocyanate (1943-83-5) + ethyl pipecolate (15862-72-3) → 1-(2-Chloro-ethylcarbamoyl)-piperidine-2-carboxylic acid ethyl ester (181948-90-3)

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

(3-nitrophenyl)methanesulfonyl chloride (58032-84-1) + ethyl pipecolate (15862-72-3) → ethyl 1-((3-nitrobenzyl)sulfonyl)piperidine-2-carboxylate

Conditions	Yield
With NMM or DIPEA In dichloromethane at 0℃;	93%

bis(trichloromethyl) carbonate (32315-10-9) + ethyl pipecolate (15862-72-3) + tert-butyl 2-{4-[(acetylamino)methyl]benzyl}-1-hydrazine carboxylate (583845-15-2) → ethyl 1-{[1-{4-[(acetylamino)methyl]benzyl}-2-(tert-butoxycarbonyl)hydrazino]carbonyl}-2-piperidinecarboxylate

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; tert-butyl 2-{4-[(acetylamino)methyl]benzyl}-1-hydrazine carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: ethyl pipecolate In dichloromethane at 20℃; for 0.5h;	91%

2-oxo-2,3-dihydro-1,3-benzothiazole-6-sulfonyl chloride (62425-99-4) + ethyl pipecolate (15862-72-3) → ethyl 1-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-ylsulfonyl)piperidine-2-carboxylate (1432733-52-2)

Conditions	Yield
Stage #1: ethyl pipecolate With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere; Stage #2: 2-oxo-2,3-dihydro-1,3-benzothiazole-6-sulfonyl chloride In dichloromethane at 20℃; Inert atmosphere;	91%
With N-ethyl-N,N-diisopropylamine at 20℃;	91%
With N-ethyl-N,N-diisopropylamine at 20℃;	91%

ethyl pipecolate (15862-72-3) + 1,3-benzothiazole-6-sulfonyl chloride (181124-40-3) → ethyl 1-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-ylsulfonyl)piperidine-2-carboxylate (1432733-52-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 20℃;	91%

formaldehyd (50-00-0) + ethyl pipecolate (15862-72-3) → ethyl 1-(methyl-d)piperidine-2-carboxylate

Conditions	Yield
With dideuterioformic acid; water-d2 In water at 85℃; for 3h; Inert atmosphere;	91%

1,3-Diphenylcarbodiimide (622-16-2) + ethyl pipecolate (15862-72-3) → 2-phenyl-3-(phenylimino)hexahydroimidazo[1,5-a]pyridin-1(5H)-one

Conditions	Yield
With tris(bis(trimethylsilyl)amido)lanthanum(III) In neat (no solvent) at 100℃; for 24h; Schlenk technique; Inert atmosphere;	91%

Carbonyldiimidazole (64269-79-0) + t-butoxycarbonylhydrazine (870-46-2) + ethyl pipecolate (15862-72-3) → (hexahydro-1,3-dioxoimidazol[1,5-a]pyridin-2(3H)-yl)-carbamic acid 1,1-dimethylethyl ester

Conditions	Yield
Stage #1: Carbonyldiimidazole; t-butoxycarbonylhydrazine In 1,4-dioxane at 20℃; for 2h; Stage #2: ethyl pipecolate In 1,4-dioxane at 60 - 70℃; for 4h;	90%

4-bromoethylbutanoate (2969-81-5) + ethyl pipecolate (15862-72-3) → ethyl 1-(4-ethoxy-4-oxo-butyl)piperidine-2-carboxylate (15912-44-4, 55302-38-0)

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 16h; Inert atmosphere;	89.8%
With potassium carbonate
With potassium carbonate In acetonitrile at 60℃; for 10h;

3-nitrobenzenesulphonyl chloride (121-51-7) + ethyl pipecolate (15862-72-3) → ethyl 1-((3-nitrophenyl)sulfonyl)piperidine-2-carboxylate (1260218-29-8)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 6h;	89%
With triethylamine; N,N-dimethyl-formamide at 20℃; for 6h;	89%

ethyl pipecolate (15862-72-3) + (4-nitrophenyl)methanesulfonyl chloride (4025-75-6) → ethyl 1-((4-nitrobenzyl)sulfonyl)piperidine-2-carboxylate

Conditions	Yield
With NMM or DIPEA In dichloromethane at 0℃;	88%

4-methylnicotinic acid (3222-50-2) + ethyl pipecolate (15862-72-3) → 1-(4-methyl-pyridine-3-carbonyl)-piperidine-2-carboxylic acid ethyl ester (1214999-42-4)

Conditions	Yield
With 4-methyl-morpholine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In dichloromethane at 20℃; for 18h;	88%

4-chlorophenyloxyacetyl chloride (4122-68-3) + ethyl pipecolate (15862-72-3) → 1-(2-(4-chlorophenoxy)acetyl)piperidine-2-carboxylate

Conditions	Yield
With NMM or DIPEA In dichloromethane at 0℃;	87%

bis(trichloromethyl) carbonate (32315-10-9) + tert-butyl 2-(4-cyanobenzyl)-1-hydrazine carboxylate (149267-90-3) + ethyl pipecolate (15862-72-3) → ethyl 1-{[2-(tert-butoxycarbonyl)-1-(4-cyanobenzyl)hydrazino]carbonyl}-2-piperidinecarboxylate

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; tert-butyl 2-(4-cyanobenzyl)-1-hydrazine carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: ethyl pipecolate In dichloromethane at 20℃; for 0.5h;	86%

ethyl pipecolate (15862-72-3) + benzenesulfonyl chloride (1939-99-7) → ethyl 1-(benzylsulfonyl)piperidine-2-carboxylate (1039510-65-0)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 6h;	86%
With triethylamine; N,N-dimethyl-formamide at 20℃; for 6h;	86%
With NMM or DIPEA In dichloromethane at 0℃;

N-(Mesyloxy)-2-carbethoxy-N-methylacetamide (164933-11-3) + ethyl pipecolate (15862-72-3) → 1-(Ethoxycarbonylmethyl-methyl-carbamoyl)-piperidine-2-carboxylic acid ethyl ester

Conditions	Yield
In dichloromethane 1.) 0 deg C, 1 h, 2.) r.t.;	84%

methanesulfonyl chloride (124-63-0) + ethyl pipecolate (15862-72-3) → ethyl 1-(methylsulfonyl)piperidine-2-carboxylate

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	84%

1-chloromethylnaphthalene (2506-41-4) + ethyl pipecolate (15862-72-3) → ethyl N-(2-naphthylmethyl)-2-piperidinecarboxylate (105855-20-7)

Conditions	Yield
In benzene for 3h; Heating;	83%

p-methoxybenzyl chloride (824-94-2) + ethyl pipecolate (15862-72-3) → 1-[(4-methoxyphenyl)methyl]piperidine-2-carboxylic acid ethyl ester (148729-20-8)

Conditions	Yield
With sodium carbonate In dichloromethane; water at 20℃; for 24h;	82%

3-chloro-n-propanesulfonyl chloride (1633-82-5) + ethyl pipecolate (15862-72-3) → ethyl 1-[(3-chloropropyl)sulfonyl]piperidine-2-carboxylate (935760-65-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 12h;	81%
With triethylamine In tetrahydrofuran at 0 - 20℃; for 12h;	81%

Upstream product

• 64-17-5 ethanol 
• 4043-87-2 pipecolic Acid 
• 98-98-6 2-Picolinic acid 
• 2524-52-9 ethyl-2-picolinate 

Downstream Products

• 109506-26-5 1-hippuroyl-piperidine-2-carboxylic acid 
• 78348-46-6 N-benzoyl-2-piperidinecarboxylic acid 
• 18391-75-8 2-phenyl-3-thioxo-hexahydro-imidazo[1,5-a]pyridin-1-one 
• 856839-85-5 (+/-)-piperidine-2-carboxylic acid ethylamide 
• 53941-92-7 N-methyl-2-piperidinecarboxamide 
• 6496-16-8 1-veratryl-piperidine-2-carboxylic acid ethyl ester 
• 3433-37-2 piperidin-2-ylmethanol 
• 19889-77-1 (RS)-piperidine-2-carboxamide 
• 148729-20-8 1-[(4-methoxyphenyl)methyl]piperidine-2-carboxylic acid ethyl ester 
• 4043-87-2 pipecolic Acid 
• 1036726-35-8 C₁₆H₂₀N₂O₆ 
• 1221440-41-0 C₁₈H₂₇NO₄ 
• 1380168-26-2 C₁₇H₂₁NO₆ 

Relevant articles and documents

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Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei

The bacteria Burkholderia pseudomallei and Legionella pneumophila cause severe diseases like melioidosis and Legionnaire's disease with high mortality rates despite antibiotic treatment. Due to increasing antibiotic resistances against these and other Gram-negative bacteria, alternative therapeutical strategies are in urgent demand. As a virulence factor, the macrophage infectivity potentiator (Mip) protein constitutes an attractive target. The Mip proteins of B. pseudomallei and L. pneumophila exhibit peptidyl-prolyl cis/trans isomerase (PPIase) activity and belong to the PPIase superfamily. In previous studies, the pipecolic acid moiety proved to be a valuable scaffold for inhibiting this PPIase activity. Thus, a library of pipecolic acid derivatives was established guided by structural information and computational analyses of the binding site and possible binding modes. Stability and toxicity considerations were taken into account in iterative extensions of the library. Synthesis and evaluation of the compounds in PPIase assays resulted in highly active inhibitors. The activities can be interpreted in terms of a common binding mode obtained by docking calculations.

A new and convenient synthesis of 1-benzyl-1-azaspiro [5.5] undecan-7-one: A formal synthesis of (±)-perhydrohistrio-nicotoxin

A rapid, three-step synthesis of the title compound 3 in 40% overall yield from (±)-pipecolinic acid, is described.