(3R,4S)-3-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane

Base Information

• Chemical Name: (3R,4S)-3-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane
• CAS No.: 140111-52-0
• Molecular Formula: C₁₁H₁₃ClN₂
• Molecular Weight: 208.691
• European Community (EC) Number: 634-286-9
• Wikipedia: Epibatidine
• Mol file: 140111-52-0.mol

Synonyms:epibatidine

Chemical Property of (3R,4S)-3-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane

Chemical Property:

• Vapor Pressure: 0.00011mmHg at 25°C
• Boiling Point: 336.7°Cat760mmHg
• PKA: 10.07±0.40(Predicted)
• Flash Point: 157.4°C
• PSA: 24.92000
• Density: 1.223g/cm³
• LogP: 2.67170
• Storage Temp.: Desiccate at +4°C
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 208.0767261
• Heavy Atom Count: 14
• Complexity: 221

Purity/Quality:

97% ^*data from raw suppliers

(+)-Epibatidine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC2C(CC1N2)C3=CN=C(C=C3)Cl
• Isomeric SMILES: C1CC2C[C@@H]([C@H]1N2)C3=CN=C(C=C3)Cl
• Uses: (+)-Epibatidine has binding affinities for α4β2 and α3β4 nicotinic receptors.

Technology Process of (3R,4S)-3-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane

There total 124 articles about (3R,4S)-3-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.0%

(1R,2R,4R)-4-bromo-2-(6-chloropyridin-3-yl)cyclohexanamine (217323-82-5) → epibatidine (140111-52-0)

Guidance literature:

In chloroform; for 72h; Heating;

DOI:10.1016/S0040-4039(98)00803-X DOI:10.1021/jo9813078

Reference yield: 92.0%

C12H14N2O2 → epibatidine (140111-52-0)

Guidance literature:

With hydrogenchloride; In methanol;

DOI:10.1039/c4ra00770k

Reference yield: 85.0%

2-choro-5-iodopyridine (69045-79-0) + oxalyl dichloride (79-37-8) + 7-azabicyclo[2.2.1]hept-2-ene → epibatidine (140111-52-0)

Guidance literature:

2-choro-5-iodopyridine; oxalyl dichloride; 7-azabicyclo[2.2.1]hept-2-ene; With piperidine; formic acid; tetrakis(triphenylphosphine) palladium⁽⁰⁾; In DMF (N,N-dimethyl-formamide); at 75 ℃; for 48h;

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 3h;

upstream raw materials:

(+)-N-(Trifluoroacetyl)epibatidine

(1S,2R,4S)-methanesulfonic acid 4-amino-2-(6-chloropyridin-3-yl)cyclohexyl ester

(1R,2R,4R)-4-bromo-2-(6-chloropyridin-3-yl)cyclohexanamine

allyl (4E)-2-[(1R)-1-(6-chloropyridin-3-yl)-2-nitroethyl]-5-methoxy-3-oxo-4-pentenoate

Refernces

α-iodocycloalkenones: Synthesis of (±)-epibatidine

10.1016/S0040-4039(98)00187-7

The study presents a total synthesis of the non-opiate analgesic alkaloid epibatidine, starting from 1,3-cyclohexadiene and achieving the final product in 13 steps with a 13% overall yield. Key chemicals involved include a-iodocyclohexenone (7), which is crucial for the Stille coupling reaction with pyridylstannane (11) to introduce the pyridyl subunit onto the central six-carbon skeleton. The synthesis involves generating an in situ nitroso reagent that undergoes cycloaddition with 1,3-cyclohexadiene to form an intermediate, which is then reduced and oxidized to obtain the enone. The pyridylstannane is prepared through a series of transformations starting from 2-methoxypyridine. The Stille coupling reaction, catalyzed by Pd[(o-tolyl)3P]2Cl2, is a pivotal step yielding the functionalized enone (12) in excellent yield. Subsequent steps involve hydrogenation, protection, and cyclization to ultimately obtain epibatidine. The study highlights the utility of transition-metal catalyzed coupling strategies in the synthesis of complex natural products.