tert-butyl (3S,4S)-4-[[(R)-tert-butylsulfinyl]amino]-3-methyl-2-oxa-8-azaspiro[4.5]decane-8-carboxylate
[CAS# 1801766-78-8]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: tert-butyl (3S,4S)-4-[[(R)-tert-butylsulfinyl]amino]-3-methyl-2-oxa-8-azaspiro[4.5]decane-8-carboxylate
• Molecular Formula: C₁₈H₃₄N₂O₄S
• Molecular Weight: 374.54
• CAS Registry Number: 1801766-78-8
• SMILES: C[C@H]1[C@H](C2(CCN(CC2)C(=O)OC(C)(C)C)CO1)N[S@](=O)C(C)(C)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 491.1±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 250.8±31.5 ºC (Calc.)^*
• Index of refraction: 1.539 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

The chemical substance tert-butyl (3S,4S)-4-[[(R)-tert-butylsulfinyl]amino]-3-methyl-2-oxa-8-azaspiro[4.5]decane-8-carboxylate is a chiral spirocyclic compound featuring a Boc-protected piperidine, a chiral sulfinamide, and an oxazolidine ring, widely used as a synthetic intermediate in pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in advancements in spirocyclic synthesis, chiral auxiliary chemistry, and protecting group strategies.

The origins of this compound are linked to the study of spirocycles, which have been explored since the early 20th century for their rigid, three-dimensional structures that enhance binding specificity in drug design. The spiro[4.5]decane framework, combining a five-membered ring with a six-membered piperidine, gained attention in the mid-20th century for its conformational stability. The tert-butoxycarbonyl (Boc) protecting group, introduced in the 1950s by Louis Carpino, became a cornerstone for amine protection due to its stability and ease of removal. The (R)-tert-butylsulfinyl group, developed in the 1990s by Jonathan Ellman, emerged as a powerful chiral auxiliary for stereoselective amine synthesis. The integration of these elements with a chiral oxazolidine ring and specific (3S,4S) stereochemistry in a spirocyclic system appeared in the late 20th and early 21st centuries, driven by the pharmaceutical industry’s need for enantiopure intermediates with complex architectures.

Synthetically, this compound is prepared through a multi-step process. A typical route starts with a spirocyclic precursor, such as 2-oxa-8-azaspiro[4.5]decan-4-one, synthesized via cyclization of a piperidine derivative with an oxygenated five-membered ring precursor. The piperidine nitrogen is protected with di-tert-butyl dicarbonate to introduce the Boc group. The chiral (3S,4S)-3-methyl-4-amino functionality is installed through stereoselective addition of a methyl group and an amine, often using (R)-tert-butylsulfinamide as a chiral auxiliary. For example, a ketone precursor is reacted with (R)-tert-butylsulfinamide to form a sulfinylimine, followed by stereoselective reduction or nucleophilic addition to achieve the (3S,4S) configuration. These steps rely on well-established protocols in spirocycle synthesis, chiral auxiliary chemistry, and Boc protection, ensuring high stereochemical purity and yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The spirocyclic core provides a rigid scaffold that enhances selectivity in binding to biological targets, such as enzymes or receptors. The Boc-protected piperidine allows selective transformations, with the nitrogen available for alkylation or amide formation after deprotection. The chiral (R)-tert-butylsulfinylamino group serves as a precursor to a free amine, enabling the construction of stereospecific amines or heterocycles, while the (3S,4S) stereochemistry ensures enantioselective interactions critical for drug efficacy. This compound is used in the synthesis of drug candidates, including kinase inhibitors, opioid receptor modulators, and anti-inflammatory agents, where the combination of chiral and polar groups optimizes pharmacokinetic properties and target affinity.

In academic research, the compound is employed to study spirocyclic synthesis, chiral sulfinamide reactivity, and stereoselective transformations. Its synthesis has contributed to the refinement of chiral auxiliary methods and oxazolidine chemistry. The compound also finds use in the synthesis of specialty chemicals, such as chiral ligands, where the spirocyclic framework and stereochemistry are advantageous.

The significance of tert-butyl (3S,4S)-4-[[(R)-tert-butylsulfinyl]amino]-3-methyl-2-oxa-8-azaspiro[4.5]decane-8-carboxylate lies in its role as a chiral, multifunctional intermediate that combines the rigidity of spirocycles with the stereospecificity of sulfinamides and Boc protection. Its development reflects progress in asymmetric synthesis and heterocyclic chemistry. By enabling the efficient synthesis of enantiopure, biologically active molecules, it has become a critical tool in advancing pharmaceutical and chemical research.