522-60-1

Basic information

• Product Name: ETHYLHYDROCUPREINE
• Synonyms: optochin;optoquine;ethylhydrocupreine free base*crystalline;Numoquine;Optochine;Ethylhydrocuprein;Hydrocupureine ethyl ether;Cinchonan-9-ol,6'-ethoxy-10,11-dihydro-, (8a,9R)-
• CAS NO: 522-60-1
• Molecular Formula: C₂₁H₂₈N₂O₂
• Molecular Weight: 340.46
• EINECS: 208-333-5
• Product Categories: Miscellaneous
• Mol File: 522-60-1.mol

Chemical Properties

• Melting Point: 123-128° when solvent-free
• Boiling Point: 476.25°C (rough estimate)
• Flash Point: 261.5°C
• Appearance: /
• Density: 1.1027 (rough estimate)
• Vapor Pressure: 3.59E-11mmHg at 25°C
• Refractive Index: 1.6180 (estimate)
• Storage Temp.: 2-8°C
• CAS DataBase Reference: ETHYLHYDROCUPREINE(CAS DataBase Reference)
• NIST Chemistry Reference: ETHYLHYDROCUPREINE(522-60-1)
• EPA Substance Registry System: ETHYLHYDROCUPREINE(522-60-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: MW5950000
• Hazardous Substances Data: 522-60-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
ETHYLHYDROCUPREINE is used as an antibiotic for testing against isolates of Streptococcus mitis, which results in 100% resistance. This property makes it a valuable tool in the development of new antibiotics and understanding bacterial resistance mechanisms.
Used in Diagnostic Applications:
In the field of medical diagnostics, ETHYLHYDROCUPREINE susceptibility test is employed as a key method for differentiating Streptococcus pneumoniae from other α-hemolytic streptococci. This helps in accurate identification and treatment of the specific bacterial infection.
Used in Research and Development:
ETHYLHYDROCUPREINE is also used in research and development for studying its potential applications in various industries, such as pharmaceuticals, due to its unique chemical structure and properties. Further research may lead to the discovery of new uses and applications for ETHYLHYDROCUPREINE.

InChI:InChI=1/C21H28N2O2/c1-3-14-13-23-10-8-15(14)11-20(23)21(24)17-7-9-22-19-6-5-16(25-4-2)12-18(17)19/h5-7,9,12,14-15,20-21,24H,3-4,8,10-11,13H2,1-2H3/t14-,15-,20-,21+/m0/s1

Synthetic route

ethyl bromide (74-96-4) + (8α,9R)-10,11-dihydro-cinchonan-6',9-diol (5962-19-6) → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
Stage #1: (8α,9R)-10,11-dihydro-cinchonan-6',9-diol With caesium carbonate In N,N-dimethyl-formamide for 0.166667h; Stage #2: ethyl bromide In N,N-dimethyl-formamide for 3h;	63%

diethyl sulfate (64-67-5) + (8α,9R)-10,11-dihydro-cinchonan-6',9-diol (5962-19-6) → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
With potassium hydroxide

chloroethane (75-00-3) + (8α,9R)-10,11-dihydro-cinchonan-6',9-diol (5962-19-6) → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
With sodium ethanolate at 75℃; im Autoklaven;

O(6')-ethyl-cupreine → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
durch katalytische Hydrierung;

sulfate ethylhydrocupreine-1-oxide → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
With sulphurous acid at 80℃; im Autoklaven;

Quinine (130-95-0) → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: palladium on carbon; hydrogen / 72 h 2.1: sodium hydride; ethanethiol / mineral oil; N,N-dimethyl-formamide / 13 h / 100 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.17 h 3.2: 3 h View Scheme

dihydroquinine (522-66-7) → (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride; ethanethiol / mineral oil; N,N-dimethyl-formamide / 13 h / 100 °C 2.1: caesium carbonate / N,N-dimethyl-formamide / 0.17 h 2.2: 3 h View Scheme

sulfuric acid (7664-93-9) + (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1) + CrO3 → 6-ethoxy-quinoline-4-carboxylic acid (525-39-3)

sulfuric acid (7664-93-9) + (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1) + potassium nitrate → 5'-nitro-ethylhydrocupreinesulfuric acid

(R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1) + chromium trioxide → 6-ethoxy-cinchoninic acid chloride

Conditions	Yield
durch Behandeln mit Thionylchlorid;

dihydrogen peroxide (7722-84-1) + (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1) → ethylhydrocupreine-1-oxide

selenium(IV) oxide (7446-08-4) + sulfuric acid (7664-93-9) + (R)-4-((1S,2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)hydroxymethyl-6-ethoxyquinoline (522-60-1) → selenoethylhydrocupreine

Conditions	Yield
folgend Verduennen mit Wasser;

Upstream product

• 64-67-5 diethyl sulfate 
• 73522-75-5 4-((S)-((1S,2R,4S,5R)-5-ethylquinuclidin-2-yl)(hydroxy)methyl)quinolin-6-ol 
• 5962-19-6 (8α,9R)-10,11-dihydro-cinchonan-6',9-diol 
• 75-00-3 chloroethane 
• 74-96-4 ethyl bromide 
• 130-95-0 Quinine 
• 522-66-7 dihydroquinine 

Downstream Products

• 525-39-3 6-ethoxy-quinoline-4-carboxylic acid 

Relevant articles and documents

A Cinchona Alkaloid Antibiotic That Appears to Target ATP Synthase in Streptococcus pneumoniae

Optochin, a cinchona alkaloid derivative discovered over 100 years ago, possesses highly selective antibacterial activity toward Streptococcus pneumoniae. Pneumococcal disease remains the leading source of bacterial pneumonia and meningitis worldwide. The structure-activity relationships of optochin were examined through modification to both the quinoline and quinuclidine subunits, which led to the identification of analogue 48 with substantially improved activity. Resistance and molecular modeling studies indicate that 48 likely binds to the c-ring of ATP synthase near the conserved glutamate 52 ion-binding site, while mechanistic studies demonstrated that 48 causes cytoplasmic acidification. Initial pharmacokinetic and drug metabolism analyses of optochin and 48 revealed limitations of these quinine analogues, which were rapidly cleared, resulting in poor in vivo exposure through hydroxylation pendants to the quinuclidine and O-dealkylation of the quinoline. Collectively, the results provide a foundation to advance 48 and highlight ATP synthase as a promising target for antibiotic development.