(7a,17a)-17-Hydroxy-3-oxo-pregna-4,9(11)-diene-7,21-dicarboxylicacid g-lactone methyl ester
[CAS# 95716-70-4]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: (7a,17a)-17-Hydroxy-3-oxo-pregna-4,9(11)-diene-7,21-dicarboxylicacid g-lactone methyl ester
• Synonyms: delta9,11-Eplerenone; methyl (7R,8R,10S,13S,14S,17R)-10,13-dimethyl-3,5'-dioxospiro[2,6,7,8,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-17,2'-oxolane]-7-carboxylate
• Molecular Formula: C₂₄H₃₀O₅
• Molecular Weight: 398.49
• CAS Registry Number: 95716-70-4
• EC Number: 619-164-5
• SMILES: C[C@]12CCC(=O)C=C1C[C@H]([C@@H]3C2=CC[C@]4([C@H]3CC[C@@]45CCC(=O)O5)C)C(=O)OC

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 580.2±50.0 ºC 760 mmHg (Calc.)^*
• Flash point: 251.7±30.2 ºC (Calc.)^*
• Index of refraction: 1.576 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H317-H319
• Precautionary Statements: P280-P305+351+338

Discovory and Applicatios

(1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol is a chiral bicyclic amine–alcohol with a partially saturated naphthalene core bearing an amino group at C-4 and a hydroxyl at C-1. The molecule’s architecture combines a rigid, hydrogen-bonding framework with stereochemical complexity, making it a valuable intermediate in the preparation of bioactive compounds and ligands for asymmetric synthesis.

Its stereochemistry was originally established through enantioselective hydrogenation of substituted naphthalenones or via resolution of racemic precursors. Once synthesized, the amine and alcohol groups can be selectively manipulated, enabling the construction of functionalized derivatives. For example, the amino group may be derivatized via acylation, sulfonamide formation, or heterocycle synthesis, while the hydroxyl group can be converted into ethers, esters, or aldehydes under mild conditions, preserving the stereochemical integrity.

One of the compound’s most important applications lies in medicinal chemistry. The 1,2,3,4-tetrahydronaphthalene motif is found in several classes of pharmacologically active molecules, including central nervous system agents, enzyme inhibitors, and receptor ligands. The chiral amino-alcohol scaffold can impart specific three-dimensional interactions with biological targets, and its rigid bicyclic core supports favorable binding conformations. Researchers often use (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol as a building block in the synthesis of lead compounds for drug discovery.

Beyond drug design, the compound is used in asymmetric catalysis and ligand development. Its dual functionality—an amine and a secondary alcohol—enables coordination with metals, making it a candidate for chiral ligand frameworks. These ligands, in turn, support enantioselective transformations such as hydrogenation, cross-coupling, or addition reactions. The scaffold’s rigidity helps ensure high enantioselectivity by limiting conformational flexibility during catalysis.

In synthetic methodology, the compound is employed to probe stereochemical outcomes and functional-group interconversions. By using protecting groups on the amine or hydroxyl, chemists can selectively activate one site for reaction while preserving the other. The scaffold’s defined chirality also allows detailed investigation of reaction mechanisms, such as stereoretentive versus stereoinvertive transformations, or the influence of stereochemistry on reactivity and regioselectivity.

Physically, (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol is typically isolated as a crystalline or viscous solid. It is moderately soluble in polar organic solvents such as methanol, ethanol, and dimethyl sulfoxide, but less soluble in nonpolar media. The compound is stable under standard laboratory conditions but should be protected from strong acids or bases, which could protonate or deprotonate its functional groups and potentially lead to racemization or degradation.

Overall, (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol is a synthetically and pharmaceutically useful chiral building block. Its rigid bicyclic scaffold and dual functional groups make it an attractive intermediate for drug design, asymmetric catalysis, and chemical methodology.

References

Eplerenone (2011) Pharmaceutical Substances. Thieme Medical Publishers, New York. (Monograph entry: Eplerenone) Link

Process to prepare eplerenone (2003) US Patent Application US-2003232981-A1. Priority date 22 March 2002. Link

Preparation method and intermediate of eplerenone (2013) Chinese Patent CN-102276684-B. Priority date 08 June 2010. Grant date 10 April 2013. Link