1193-65-3

Basic information

• Product Name: 3-Quinuclidinone hydrochloride
• Synonyms: QUINUCLIDIN-3-ONE HYDROCHLORIDE;3-AMINOQUINUCLIDINONE HYDROCHLORIDE;3-QUINUCLIDINONE HCL;3-QUINUCLIDINONE HYDROCHLORIDE;3-QUINUCLIDONE HYDROCHLORIDE;1-AZA-3-OXOBICYCLO[2.2.2]OCTANE HYDROCHLORIDE;1-AZABICYCLO[2.2.2]OCTAN-3-ONE HYDROCHLORIDE;3-Quinuclidione HCl
• CAS NO: 1193-65-3
• Molecular Formula: C₇H₁₂NO*Cl
• Molecular Weight: 161.63
• EINECS: 214-776-5
• Product Categories: Pharmaceutical material and intermeidates;Carbonyl Compounds;Heterocycles;Quinuclidine derivatives;Ring Systems;Pharmaceutical Intermediates;Building Blocks;Chemical Synthesis;Heterocyclic Building Blocks;Quinuclidines
• Mol File: 1193-65-3.mol

Chemical Properties

• Melting Point: >300 °C (dec.)(lit.)
• Boiling Point: 204.9ºCat 760 mmHg
• Flash Point: 78.1ºC
• Appearance: White to off-white/Powder
• Vapor Pressure: 0.257mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: H2O: 0.1 g/mL, clear
• Sensitive: Hygroscopic
• BRN: 3695039
• CAS DataBase Reference: 3-Quinuclidinone hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Quinuclidinone hydrochloride(1193-65-3)
• EPA Substance Registry System: 3-Quinuclidinone hydrochloride(1193-65-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-37/39-26
• WGK Germany: 3
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 1193-65-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
3-Quinuclidinone hydrochloride is used as a key intermediate in the synthesis of cevimeline, a thiolating agent. It plays a vital role in the development of this drug, which has potential applications in treating various medical conditions.
Used in the Preparation of Cannabinoid Receptor Ligands:
3-Quinuclidinone hydrochloride is also utilized in the preparation of novel CB1 and CB2 cannabinoid receptor ligands. These ligands are essential in the development of drugs targeting the endocannabinoid system, which is involved in various physiological processes, including pain, mood, and appetite regulation.

InChI:InChI=1/C7H11NO.ClH/c9-7-5-8-3-1-6(7)2-4-8;/h6H,1-5H2;1H

Synthetic route

3-quinuclidinol (1619-34-7) → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Stage #1: 3-quinuclidinol With 1-methyl-1H-imidazole; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; 4,4'-Dimethoxy-2,2'-bipyridin; 9-azabicyclo[3.3.1]nonane N-oxyl; oxygen In acetonitrile at 70℃; for 1.5h; Stage #2: With hydrogenchloride In diethyl ether; acetonitrile for 0.5h;	82%

ethyl 1-(2-methoxy-2-oxoethyl) piperidine-4-carboxylate → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Stage #1: ethyl 1-(2-methoxy-2-oxoethyl) piperidine-4-carboxylate With potassium tert-butylate In toluene at 111℃; for 3h; Dieckmann Condensation; Inert atmosphere; Stage #2: With hydrogenchloride In water for 14h; Dieckmann Condensation; Reflux; Stage #3: With potassium carbonate In water Solvent; Reagent/catalyst; Dieckmann Condensation;	80%

(S)-quinuclidin-3-ol (3684-26-2, 25333-42-0, 34583-34-1, 1619-34-7) → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Stage #1: (S)-quinuclidin-3-ol With dimethylsulfide; triethylamine In chloroform at -15 - -10℃; Inert atmosphere; Stage #2: With N-chloro-succinimide In chloroform at -15 - -10℃; for 4h; Inert atmosphere;	79%

2-Ethoxycarbonyl-3-oxoquinuclidine oxime hydrochloride (110056-51-4) → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
With hydrogen; platinum(IV) oxide In hydrogenchloride

1-ethoxycarbonylmethyl-piperidine-4-carboxylic acid methyl ester (95566-71-5) + toluene (108-88-3) + potassium → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Erhitzen des Reaktionsgemisches mit wss. HCl;

isonipecotic acid (498-94-2) → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuryl dichloride / N,N-dimethyl-formamide / 6 h / 80 °C / Inert atmosphere 2.1: sodium carbonate / toluene / 4 h / 20 - 45 °C 3.1: potassium tert-butylate / toluene / 3 h / 111 °C / Inert atmosphere 3.2: 14 h / Reflux View Scheme

ethyl N-ethoxycarbonylmethyl-4-piperidinecarboxylate (1838-39-7) → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium tert-butylate / toluene / 4.5 h / Reflux; Inert atmosphere 2.1: Reflux 2.2: 20 °C View Scheme

2-ethoxycarbonyl-3-quinuclidinone (34286-16-3) → 3-quinuclidinone hydrochloride (1193-65-3)

Conditions	Yield
Stage #1: 2-ethoxycarbonyl-3-quinuclidinone Reflux; Stage #2: With hydrogenchloride In ethanol at 20℃;	25.4 g

3-quinuclidinone hydrochloride (1193-65-3) → 3-quinuclidone oxime (35423-17-7)

Conditions	Yield
With hydroxylamine hydrochloride; sodium acetate In water at 70℃; for 2h; Inert atmosphere;	100%
With hydroxylamine hydrochloride; sodium acetate In water at 70℃; for 1h;
With hydroxylamine hydrochloride; sodium acetate In water at 0 - 70℃; for 1h;

3-quinuclidinone hydrochloride (1193-65-3) → 3-Quinuclidinone (3731-38-2)

Conditions	Yield
With sodium carbonate; sodium hydroxide In water at 0℃; for 0.5h;	100%
With sodium hydrogencarbonate In water at 20℃; for 0.166667h;	88%
With ammonia In methanol

sodium cyanide (143-33-9) + 3-quinuclidinone hydrochloride (1193-65-3) → 3-hydroxy-1-azabicyclo[2.2.2]octane-3-carbonitrile (6238-30-8)

Conditions	Yield
In water at 0℃; for 3h;	99%

3-quinuclidinone hydrochloride (1193-65-3) + 4-phenoxyanilin (139-59-3) → N-(4-phenoxyphenyl)quinuclidin-3-amine

Conditions	Yield
With sodium tris(acetoxy)borohydride; sodium sulfate In acetic acid at 20℃; for 15h;	99%
With sodium tris(acetoxy)borohydride; acetic acid; sodium sulfate at 20℃; for 15h;	99%

potassium cyanide (151-50-8) + 3-quinuclidinone hydrochloride (1193-65-3) → 3-hydroxy-1-azabicyclo[2.2.2]octane-3-carbonitrile (6238-30-8)

Conditions	Yield
In water for 3h;	98%
With water

3-quinuclidinone hydrochloride (1193-65-3) + p-aminoiodobenzene (540-37-4) → N-(4-iodophenyl)quinuclidin-3-amine (854935-45-8)

Conditions	Yield
With sodium tris(acetoxy)borohydride; sodium sulfate In acetic acid at 20℃; for 15h;	98%
With sodium tris(acetoxy)borohydride; sodium sulfate In acetic acid at 20℃; for 15h;	98%
	98%
With sodium tris(acetoxy)borohydride; acetic acid; sodium sulfate at 20℃; for 15h;	98%
With NaBH(OAc)3; sodium hydrogencarbonate; sodium sulfate In acetic acid

3-quinuclidinone hydrochloride (1193-65-3) → 3-hydroxy-1-azabicyclo[2.2.2]octane-3-carbonitrile (6238-30-8)

Conditions	Yield
In water	97%
In water
In 1,4-dioxane; water

3-pyridinecarboxaldehyde (500-22-1) + 3-quinuclidinone hydrochloride (1193-65-3) → (±)-2-(pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one (273748-55-3)

Conditions	Yield
With potassium hydroxide In methanol at 20℃; for 16h;	96%
Stage #1: 3-quinuclidinone hydrochloride With potassium hydroxide In methanol at 50 - 56℃; for 2h; Industry scale; Stage #2: 3-pyridinecarboxaldehyde In methanol at 20℃; for 12h; Product distribution / selectivity; Industry scale;	89.3%
Stage #1: 3-quinuclidinone hydrochloride With potassium hydroxide In methanol at 20℃; for 0.5h; Stage #2: 3-pyridinecarboxaldehyde In methanol at 20℃; for 16h; Product distribution / selectivity;	82%
With sodium hydroxide In methanol at 20℃; for 24h;	67%

methanol (67-56-1) + trimethylsulfoxonium iodide (1774-47-6) + 3-quinuclidinone hydrochloride (1193-65-3) → 3-Methoxymethylquinuclidine-3-ol (242810-00-0)

Conditions	Yield
With sodium hydroxide for 1h; Addition; Etherification; Heating;	95%

3-quinuclidinone hydrochloride (1193-65-3) + 4-(4-methylphenoxy)aniline (41295-20-9) → N-[4-(4-methylphenoxy)phenyl]quinuclidin-3-amine (854935-41-4)

Conditions	Yield
	95%

3-quinuclidinone hydrochloride (1193-65-3) → 3-quinuclidinol (1619-34-7)

Conditions	Yield
Stage #1: 3-quinuclidinone hydrochloride With water; sodium hydroxide at -5 - 0℃; for 0.5h; Stage #2: With sodium tetrahydroborate In water for 1.5h; Further stages;	94.7%
With water; nickel under 36775.4 - 73550.8 Torr; Hydrogenation;
With sodium hydroxide; water; nickel under 88260.9 Torr; Hydrogenation;

3-quinuclidinone hydrochloride (1193-65-3) + (1,2-dihydronaphthalen-4-yl)methanamine hydrochloride (80096-46-4) → N-[(3,4-dihydronaphthalen-1-yl)methyl]-(S)-1-azabicyclo[2.2.2]octan-3-amine

Conditions	Yield
Stage #1: 3-quinuclidinone hydrochloride; (1,2-dihydronaphthalen-4-yl)methanamine hydrochloride With triethylamine In toluene for 4h; Reflux; Stage #2: With sodium tetrahydroborate In butan-1-ol at 0 - 20℃; for 4h;	93.2%

3-quinuclidinone hydrochloride (1193-65-3) → (R)-quinuclidin-3-ol (25333-42-0)

Conditions	Yield
With D-glucose In aq. phosphate buffer at 37℃; for 30h; pH=8; Concentration; Temperature; pH-value; Time;	93%
Multi-step reaction with 2 steps 1: sodium; ethanol 2: (1S)-2-oxo-bornane-10-sulfonic acid View Scheme
With R-DAIPEN; potassium tert-butylate; hydrogen; [RuCl(p-cymene)((R)-DM-SEGPHOS)]Cl In isopropyl alcohol at 30℃; under 22502.3 Torr; for 8h; Conversion of starting material;	n/a

3-quinuclidinone hydrochloride (1193-65-3) + 4-amino-4'-chlorodiphenyl ether (101-79-1) → N-[4-(4-chlorophenoxy)phenyl]quinuclidin-3-amine (854935-39-0)

Conditions	Yield
	93%

3-quinuclidinone hydrochloride (1193-65-3) + 4-dimethylamino-benzaldehyde (100-10-7) → 2-(4-dimethylaminobenzylidene)-1-azabicyclo[2.2.2]octan-3-one (196712-97-7)

Conditions	Yield
With sodium hydroxide In ethanol; water for 0.5h; Claisen-Schmidt condensation; Heating;	92.8%
With sodium hydroxide In ethanol Condensation; Heating;	61%

3-quinuclidinone hydrochloride (1193-65-3) → (S)-quinuclidin-3-ol (3684-26-2, 25333-42-0, 34583-34-1, 1619-34-7)

Conditions	Yield
With D-glucose In aq. phosphate buffer at 30℃; for 48h; pH=8; Concentration; Temperature; pH-value; Time;	92%
Multi-step reaction with 2 steps 1: sodium; ethanol 2: (1S)-2-oxo-bornane-10-sulfonic acid View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide; water / 0.5 h / -5 - 0 °C 1.2: 1.5 h 2.1: 2 h / 20 °C 3.1: ethanol; water / 0.33 h / 50 °C 4.1: sodium hydroxide / water / 1 h / 70 °C View Scheme

3-quinuclidinone hydrochloride (1193-65-3) + benzaldehyde (100-52-7) → (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one (24123-89-5)

Conditions	Yield
With sodium hydroxide In ethanol; water for 0.5h; Claisen-Schmidt condensation; Heating;	90%
With water; sodium hydroxide Reflux; Large scale;	88.9%
With sodium hydroxide In ethanol for 2h; Reflux;	87%

3-quinuclidinone hydrochloride (1193-65-3) + ortho-anisaldehyde (135-02-4) → (Z)-2-(2-methoxybenzylidene)quinuclidin-3-one (196712-90-0)

Conditions	Yield
With sodium hydroxide In ethanol Condensation; Heating;	90%
With sodium hydroxide In ethanol for 4h; Reflux;	82%

potassium cyanide (151-50-8) + ammonium carbonate (506-87-6) + 3-quinuclidinone hydrochloride (1193-65-3) → 4-azaspiro[bicyclo[2.2.2]octane-2,4'-imidazolidine]-2',5'-dione (37874-20-7)

Conditions	Yield
In ethanol at 60℃; for 24h; sealed flask;	88%

3-quinuclidinone hydrochloride (1193-65-3) + ethyl 2-cyanoacetate (105-56-6) → ethyl (1-azabicyclo<2.2.2>octan-3-ylidene)cyanoacetate hydrochloride

Conditions	Yield
With triethylamine at 75℃;	88%

O-ethylhydroxylamine hydrochloride (3332-29-4) + 3-quinuclidinone hydrochloride (1193-65-3) → 1-azabicyclo[2.2.2]octan-3-one O-ethyloxime

Conditions	Yield
In methanol for 3h; Heating;	87%

3-quinuclidinone hydrochloride (1193-65-3) + phenoxyamine hydrochloride (6092-80-4) → 1-azabicyclo[2.2.2]octan-3-one O-phenyloxime

Conditions	Yield
In methanol for 3h; Heating;	87%

ferrocenecarboxaldehyde (12093-10-6) + 3-quinuclidinone hydrochloride (1193-65-3) → 2-ferrocenylmethylenequinuclidone

Conditions	Yield
In ethanol; water elem. anal.;	85%

3-quinuclidinone hydrochloride (1193-65-3) → Quinuclidine (100-76-5)

Conditions	Yield
With potassium hydroxide; hydrazine In diethylene glycol at 160℃; for 3h;	84%
Multi-step reaction with 3 steps 1: NaOH-solution; Raney nickel; water / 88260.9 Torr / Hydrogenation 2: thionyl chloride / Anschliessend Erwaermen 3: Raney nickel; sodium methylate; methanol / 60 °C / 73550.8 Torr / Hydrogenation View Scheme

6-nitroindole (4769-96-4) + 3-quinuclidinone hydrochloride (1193-65-3) → 3-(6-nitro-1H-indol-3-yl)-1-azabicyclo[2.2.2]oct-2-ene (954387-20-3)

Conditions	Yield
With potassium hydroxide In methanol; water for 36h; Inert atmosphere; Reflux;	84%

thiophene-2-carbaldehyde (98-03-3) + 3-quinuclidinone hydrochloride (1193-65-3) → 2-(thiophen-2-ylmethylene)-1-azabicyclo[2.2.2]octan-3-one (82955-33-7)

Conditions	Yield
With sodium hydroxide In ethanol; water for 0.5h; Claisen-Schmidt condensation; Heating;	83.7%

3-quinuclidinone hydrochloride (1193-65-3) → 1-azabicyclo<2.2.2>octan-3-one oxime (78961-49-6)

Conditions	Yield
With hydroxylamine hydrochloride; sodium acetate In ethanol at 20℃; for 18h;	83%

3-quinuclidinone hydrochloride (1193-65-3) + 4-chlorobenzaldehyde (104-88-1) → (Z)-2-(4-chlorobenzylidene)quinuclidin-3-one

Conditions	Yield
With sodium hydroxide In ethanol for 2h; Reflux;	83%

3-pyridinecarboxaldehyde (500-22-1) + 3-quinuclidinone hydrochloride (1193-65-3) → 2-((pyridin-3-yl)methyl)-1-azabicyclo[2.2.2]octan-3-one (273748-51-9)

Conditions	Yield
Stage #1: 3-quinuclidinone hydrochloride With potassium hydroxide In methanol at 20℃; for 0.5h; Stage #2: 3-pyridinecarboxaldehyde In methanol at 20℃; for 16h;	82%
With potassium hydroxide In methanol; water

Upstream product

• 95566-71-5 1-ethoxycarbonylmethyl-piperidine-4-carboxylic acid methyl ester 
• 108-88-3 toluene 
• 3684-26-2 (S)-quinuclidin-3-ol 
• 1619-34-7 3-quinuclidinol 
• 498-94-2 isonipecotic acid 
• 71172-59-3 ethyl 1-(2-methoxy-2-oxoethyl) piperidine-4-carboxylate 
• 1838-39-7 ethyl N-ethoxycarbonylmethyl-4-piperidinecarboxylate 
• 34286-16-3 2-ethoxycarbonyl-3-quinuclidinone 
• 110056-51-4 2-Ethoxycarbonyl-3-oxoquinuclidine oxime hydrochloride 

Downstream Products

• 6238-30-8 3-hydroxy-1-azabicyclo[2.2.2]octane-3-carbonitrile 
• 1619-34-7 3-quinuclidinol 
• 30708-54-4 1-aza-bicyclo[3.2.2]nonan-4-one 
• 37874-20-7 4-azaspiro[bicyclo[2.2.2]octane-2,4'-imidazolidine]-2',5'-dione 
• 61371-56-0 (2R,3R)-2-((S)-Hydroxy-phenyl-methyl)-1-aza-bicyclo[2.2.2]octan-3-ol 
• 60300-68-7 (S)-2-(Hydroxy-phenyl-methyl)-1-aza-bicyclo[2.2.2]octan-3-one 
• 6659-51-4 3-oxo-1-methylquinuclidinium iodide 
• 120570-06-1 N-((S)-1-phenylethyl)-3-quinuclidinimine 
• 24123-89-5 (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one 
• 78961-35-0 cis-2-(2'-Hydroxybenzylidene)-3-oxoquinuclidine 
• 78961-43-0 cis-2-(4'-Nitrobenzylidene)-3-oxoquinuclidine 
• 196712-91-1 (Z)-2-(4-hydroxyphenyl)methylene-3-quinuclidone 
• 78961-42-9 trans-2-(4-Methoxybenzylidene)-3-oxoquinuclidine 
• 196712-90-0 (Z)-2-(2-methoxybenzylidene)quinuclidin-3-one 

Relevant articles and documents

Preparation method of optical activity 3-quinuclidinol

The invention relates to an intermediate synthesis method, belongs to the field of organic synthesis, and particularly relates to a preparation method of optical activity 3-quinuclidinol with the advantages that the operation is simple and convenient, the cost is low, and the method is suitable for industrial production. An intermediate of 3-quinuclidinol is obtained by using 4-nipecotic acid as astarting material through esterification, nucleophilic substitution, Dieckmann condensation, decarboxylation, salification, reduction, acetylization, chemical resolution and the like. The reaction formula is shown in the description.

An improved and simple route for the synthesis of 3-quinuclidinone hydrochloride

An improved method for the synthesis of 3-quinuclidinone hydrochloride 4 from piperidine-4-carboxylic acid 1 has been described. Reaction of piperidine-4-carboxylic acid 1 with thionyl chloride and ethanol gave ethyl piperidine 4-carboxylate 2. It was further condensed with methyl chloroacetate in presence of sodium carbonate to give ethyl 1-(2-methoxy-2-oxoethyl)piperidine-4-carboxylate 3. One pot Dieckmann reaction of 3 in presence of potassium tertbutoxide followed by hydrolysis and decarboxylation gave title compound azabicyclo[2.2.2]oct-3-one hydrochloride 4.

Copper(I)/ABNO-catalyzed aerobic alcohol oxidation: Alleviating steric and electronic constraints of Cu/TEMPO catalyst systems

Cu/TEMPO catalyst systems promote efficient aerobic oxidation of sterically unhindered primary alcohols and electronically activated substrates, but they show reduced reactivity with aliphatic and secondary alcohols. Here, we report a catalyst system, consisting of (MeObpy)CuI(OTf) and ABNO (MeObpy =4,4′-dimethoxy-2,2′-bipyridine; ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl), that mediates aerobic oxidation of all classes of alcohols, including primary and secondary allylic, benzylic, and aliphatic alcohols with nearly equal efficiency. The catalyst exhibits broad functional group compatibility, and most reactions are complete within 1 h at room temperature using ambient air as the source of oxidant.

A process for producing 3-quinuclidinone hydrochloride by oxidation of unwanted isomer 3-S-quinuclidinol

An industrially efficient method was developed synthetic process for the preparation of 3-quinuclidinone HCl by recycling of 3-S-quinuclidinol in one step sequence of oxidation process. Oxidation of secondary alcohol of 3-S-quinuclidinol which utilises complexes of a sulfide such as dimethyl sulfide with N-chlorosuccinimide to give target compound in high yield.

SYNTHESIS AND PROPERTIES OF 2-ETHOXYCARBONYL-3-AMINO-2,3-DEHYDROQUINUCLIDINE

The reduction of 2-ethoxycarbonyl-3-oxoquinuclidine oxime hydrochloride leads to 2-ethoxycarbonyl-3-amino-2,3-dehydroquinuclidine, from which pyrimidoquinuclidine derivatives were obtained by reaction with formamide, methyl isocyanate, and phenyl isocyanate.It is shown that 7-hydroxypyrazoloquinuclidine is formed in the reaction of 2-ethoxycarbonyl-3-acetamido-2,3-dehydroquinuclidine with hydrazine hydrate.