t-Butyl (4S)-4-(methoxymethyl)-2,2-dioxo-oxathiazolidine-3-carboxylate
[CAS# 2023006-41-7]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound >> Thiazole, thiophene and pyridine
• Name: t-Butyl (4S)-4-(methoxymethyl)-2,2-dioxo-oxathiazolidine-3-carboxylate
• Molecular Formula: C₉H₁₇NO₆S
• Molecular Weight: 267.30
• CAS Registry Number: 2023006-41-7
• EC Number: 882-536-2
• SMILES: CC(C)(C)OC(=O)N1[C@H](COS1(=O)=O)COC

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 324.5±34.0 °C 760 mmHg (Calc.)^*
• Flash point: 150.0±25.7 °C (Calc.)^*
• Index of refraction: 1.484 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Discovery and Applications

The chemical substance t-butyl (4S)-4-(methoxymethyl)-2,2-dioxo-oxathiazolidine-3-carboxylate, a chiral Boc-protected cyclic sulfamidate, is a specialized heterocyclic compound valued as a synthetic intermediate in pharmaceutical chemistry. Its discovery and applications are well-documented in the literature, rooted in the development of chiral heterocycles, sulfamidate chemistry, and protecting group strategies.

The origins of this compound are linked to the study of cyclic sulfamidates, five-membered heterocycles containing sulfur, oxygen, and nitrogen, which emerged in the late 20th century as versatile intermediates due to their reactivity in nucleophilic ring-opening reactions. 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 a chiral (4S)-methoxymethyl group into a 2,2-dioxo-oxathiazolidine framework gained attention in the 1990s and 2000s, driven by the pharmaceutical industry’s need for enantiopure intermediates to synthesize complex, biologically active molecules. Advances in stereoselective synthesis, particularly in the formation of chiral sulfamidates, enabled the precise construction of such compounds.

Synthetically, t-butyl (4S)-4-(methoxymethyl)-2,2-dioxo-oxathiazolidine-3-carboxylate is prepared through a multi-step process. A typical route starts with a chiral (S)-serine derivative, such as (S)-2-amino-3-methoxypropan-1-ol, where the methoxymethyl group is introduced via methylation of the hydroxyl side chain. The amino alcohol is cyclized with thionyl chloride to form a cyclic sulfite, which is oxidized to the sulfamidate using an oxidizing agent like sodium periodate or ruthenium tetroxide. The nitrogen is then protected by reaction with di-tert-butyl dicarbonate in the presence of a base, such as triethylamine, to form the Boc-protected sulfamidate. The (4S) stereochemistry is preserved from the chiral starting material or established using a chiral auxiliary or catalyst. These steps rely on well-established protocols in chiral synthesis, sulfamidate chemistry, and Boc protection, ensuring high enantiomeric purity and yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The cyclic sulfamidate is a highly reactive electrophile, undergoing regioselective ring-opening with nucleophiles like amines, thiols, or carbon nucleophiles to form chiral amino acid derivatives or other functionalized molecules. The (4S)-methoxymethyl group provides stereospecificity and a polar handle, enhancing solubility and enabling further transformations, such as ether cleavage or substitution. The Boc group protects the nitrogen, allowing selective reactions at the sulfamidate ring, and can be removed to yield a free amine for additional functionalization. This compound is frequently used in the synthesis of drug candidates, including enzyme inhibitors, peptide mimetics, and antiviral agents, where the chiral sulfamidate facilitates the construction of stereospecific scaffolds with optimized pharmacokinetic properties.

In academic research, the compound is employed to study sulfamidate reactivity, stereoselective ring-opening reactions, and the effects of Boc protection on heterocyclic systems. Its synthesis has contributed to the development of new chiral sulfamidate methodologies and asymmetric synthesis techniques. The compound also finds use in the synthesis of specialty chemicals, such as chiral ligands or molecular probes, where the heterocyclic structure and stereochemistry are advantageous.

The significance of t-butyl (4S)-4-(methoxymethyl)-2,2-dioxo-oxathiazolidine-3-carboxylate lies in its role as a chiral, multifunctional intermediate that combines the reactivity of sulfamidates with the stereospecificity of a methoxymethyl group and Boc protection. Its development reflects progress in chiral heterocyclic 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.