Tert-butyl (8-syn)-3-azabicyclo[3.2.1]oct-8-ylcarbamate
[CAS# 847862-26-4]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Tert-butyl (8-syn)-3-azabicyclo[3.2.1]oct-8-ylcarbamate
• Molecular Formula: C₁₂H₂₂N₂O₂
• Molecular Weight: 226.32
• CAS Registry Number: 847862-26-4
• SMILES: CC(C)(C)OC(=O)NC1[C@@H]2CC[C@H]1CNC2

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 339.8±31.0 ºC 760 mmHg (Calc.)^*
• Flash point: 159.3±24.8 ºC (Calc.)^*
• Index of refraction: 1.507 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H315-H318-H335
• Precautionary Statements: P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P332+P313-P362-P403+P233-P405-P501

Discovory and Applicatios

The chemical substance tert-butyl (8-syn)-3-azabicyclo[3.2.1]oct-8-ylcarbamate, commonly referred to as Boc-protected 8-amino-3-azabicyclo[3.2.1]octane with syn stereochemistry, is a bicyclic amine derivative widely used as a synthetic intermediate in pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in the development of bicyclic amine scaffolds and protecting group chemistry.

The origins of this compound are tied to the study of bicyclic amines, such as the 3-azabicyclo[3.2.1]octane system, which have been explored since the mid-20th century for their rigid, three-dimensional structures resembling natural alkaloids. These scaffolds gained attention for their potential in medicinal chemistry due to their conformational constraints, which enhance binding specificity. The tert-butoxycarbonyl (Boc) protecting group, introduced in the 1950s by Louis Carpino, became a cornerstone for amine protection due to its stability under basic conditions and ease of removal under mild acidic conditions. The specific functionalization of the 8-position with a Boc-protected amine in the syn configuration emerged in the late 20th century, driven by the pharmaceutical industry’s need for chiral, rigid intermediates to construct bioactive molecules. Advances in stereoselective synthesis during the 1970s and 1980s enabled the precise control of the syn stereochemistry at the 8-position.

Synthetically, tert-butyl (8-syn)-3-azabicyclo[3.2.1]oct-8-ylcarbamate is prepared through a multi-step process. A typical route starts with a 3-azabicyclo[3.2.1]octane precursor, such as norbornene or a related bicyclic system, which is functionalized to introduce the piperidine-like nitrogen via hydroamination or azide reduction. The 8-position is then equipped with an amino group through stereoselective transformations, often involving epoxidation or aziridination of a bicyclic alkene, followed by ring-opening with ammonia or an amine equivalent under conditions that favor the syn configuration. The resulting 8-amino group is protected by reaction with di-tert-butyl dicarbonate in the presence of a base, such as triethylamine, to form the Boc carbamate. These steps rely on well-established bicyclic synthesis, stereoselective functionalization, and protecting group protocols, ensuring high stereochemical purity and yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The 3-azabicyclo[3.2.1]octane core provides a rigid, compact scaffold that mimics alkaloid structures, making it valuable for targeting receptors or enzymes in the central nervous system, pain management, and addiction treatment. The Boc-protected amine at the 8-position allows selective transformations at other sites, with the nitrogen available for alkylation, amide formation, or heterocycle synthesis after deprotection. The syn stereochemistry at the 8-position is critical for ensuring specific interactions with biological targets, enhancing the compound’s efficacy. This compound is frequently used in the synthesis of drug candidates, such as opioid receptor modulators, dopamine receptor agonists, and analgesic agents, where the bicyclic framework and chiral amine optimize pharmacokinetic properties and binding affinity.

In academic research, the compound is employed to study bicyclic amine synthesis, stereoselective functionalization, and the effects of Boc protection on amine reactivity. Its synthesis has contributed to the development of new stereoselective methods for bicyclic systems. The compound also finds use in the synthesis of specialty chemicals, such as chiral ligands or molecular probes, where the rigid bicyclic structure and amine functionality are advantageous.

The significance of tert-butyl (8-syn)-3-azabicyclo[3.2.1]oct-8-ylcarbamate lies in its role as a chiral, multifunctional intermediate that combines the rigidity of a bicyclic amine with the synthetic versatility of a Boc-protected amine. Its development reflects progress in stereoselective synthesis and protecting group chemistry. By enabling the efficient synthesis of enantiopure, biologically active molecules, it has become a critical tool in advancing pharmaceutical and chemical research.