Tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate
[CAS# 873924-07-3]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate
• Molecular Formula: C₁₅H₂₃NO₃
• Molecular Weight: 265.35
• CAS Registry Number: 873924-07-3
• SMILES: CC(C)(C)OC(=O)N1CCC2(CCC(=O)C=C2)CC1

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 388.9±42.0 ºC 760 mmHg (Calc.)^*
• Flash point: 189.0±27.9 ºC (Calc.)^*
• Index of refraction: 1.524 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

The chemical substance tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate is a spirocyclic piperidine derivative with a Boc-protected amine and an enone functionality, widely utilized as a synthetic intermediate in pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in the development of spirocyclic compounds and protecting group chemistry.

The origins of this compound are linked to the study of spirocycles, molecules with two rings sharing a single atom, which have been explored since the early 20th century for their rigid, three-dimensional structures. Spiro[5.5]undecane derivatives, featuring a six-membered ring fused to a cyclohexane, gained attention in the mid-20th century for their conformational stability and utility in medicinal chemistry. The tert-butoxycarbonyl (Boc) protecting group, introduced in the 1950s by Louis Carpino, became a standard for amine protection due to its stability and ease of removal under mild acidic conditions. The incorporation of an enone (a conjugated ketone with a double bond) and a Boc-protected piperidine in a spirocyclic framework emerged in the late 20th century, driven by the pharmaceutical industry’s need for complex, rigid scaffolds to enhance binding specificity in drug design. Advances in spirocycle synthesis and regioselective functionalization during the 1970s and 1980s enabled the construction of such compounds.

Synthetically, tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate is prepared through a multi-step process. A common route starts with a cyclohexanone derivative, which is spirocyclized with a piperidine precursor, such as 4-oxopiperidine, under acidic or basic conditions to form the spiro[5.5]undecane core. The nitrogen is protected by reaction with di-tert-butyl dicarbonate to introduce the Boc group. The enone functionality at the 7,9-positions is introduced via a sequence involving allylic oxidation or aldol condensation, followed by dehydration to form the conjugated double bond and ketone. Alternatively, a Diels-Alder reaction with a diene and a dienophile containing the piperidine moiety can be used to construct the spirocyclic framework, followed by functional group manipulation. These steps rely on well-established spirocycle synthesis, protecting group chemistry, and enone formation protocols, ensuring structural integrity and high yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The spirocyclic core provides a rigid, three-dimensional scaffold that enhances selectivity and binding affinity in drug molecules, making it valuable for targeting enzymes or receptors. The Boc-protected piperidine allows selective transformations at other sites, with the nitrogen available for further functionalization, such as alkylation or amide formation, after deprotection. The enone group is a reactive handle for conjugate additions, reductions, or cycloadditions, enabling the construction of complex molecular architectures. This compound is frequently used in the synthesis of drug candidates, including kinase inhibitors, G-protein-coupled receptor modulators, and analgesics, where the spirocyclic structure optimizes pharmacokinetic properties and biological activity.

In academic research, the compound is employed to study spirocycle synthesis, enone reactivity, and the effects of Boc protection on piperidine derivatives. Its synthesis has contributed to the development of new spirocyclization methods and stereoselective transformations. The compound also finds use in the synthesis of specialty chemicals, such as molecular probes or catalysts, where the rigid spirocyclic framework is advantageous.

The significance of tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate lies in its role as a multifunctional intermediate that combines the structural rigidity of spirocycles with the synthetic versatility of Boc-protected amines and enones. Its development reflects progress in spirocyclic synthesis and regioselective functionalization. By enabling the efficient synthesis of complex, biologically active molecules, it has become a critical tool in advancing pharmaceutical and chemical research.