(S)-Methanesulfonic acid 2-Boc-amino-propyl ester
[CAS# 126301-16-4]

Identification

• Classification: Biochemical >> Amino acids and their derivatives
• Name: (S)-Methanesulfonic acid 2-Boc-amino-propyl ester
• Synonyms: [(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propyl] methanesulfonate
• Molecular Formula: C₉H₁₉NO₅S
• Molecular Weight: 253.32
• CAS Registry Number: 126301-16-4
• SMILES: C[C@@H](COS(=O)(=O)C)NC(=O)OC(C)(C)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 75 - 77 ºC (Expl.)
• Boiling point: 397.9±25.0 ºC 760 mmHg (Calc.)^*
• Flash point: 194.5±23.2 ºC (Calc.)^*
• Index of refraction: 1.462 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501

Discovory and Applicatios

The compound (S)-methanesulfonic acid 2-Boc-amino-propyl ester, often referred to as a Boc-protected amino mesylate, is a chiral organic molecule widely utilized in synthetic organic chemistry, particularly in the preparation of pharmaceuticals and fine chemicals. Its development and applications are grounded in the established chemistry of protecting groups and sulfonate esters, which have been extensively studied since the mid-20th century.

The origins of this compound are tied to the evolution of the tert-butoxycarbonyl (Boc) protecting group, introduced in the 1950s by Louis Carpino and others to shield amine functionalities during complex syntheses. The Boc group’s stability under basic conditions and its facile removal under mild acidic conditions made it a cornerstone of peptide and organic synthesis. Simultaneously, methanesulfonic acid esters, or mesylates, were recognized in the early 20th century as excellent leaving groups in nucleophilic substitution reactions due to their high reactivity and stability. The specific compound, (S)-methanesulfonic acid 2-Boc-amino-propyl ester, emerged as a valuable intermediate in chiral synthesis, leveraging the stereochemical control achieved through advancements in asymmetric synthesis techniques during the 1970s and 1980s. These techniques, including the use of chiral starting materials and catalysts, enabled the production of enantiopure compounds critical for biological applications.

Synthetically, (S)-methanesulfonic acid 2-Boc-amino-propyl ester is typically prepared from (S)-alaninol or a related chiral amino alcohol. The amine group of the starting material is protected by reaction with di-tert-butyl dicarbonate to form the Boc-protected intermediate. The hydroxyl group is then converted to a mesylate by treatment with methanesulfonyl chloride in the presence of a base, such as triethylamine. This sequence ensures retention of the (S)-stereochemistry, which is essential for the compound’s applications. The resulting mesylate is a highly reactive electrophile, making it a versatile building block in organic synthesis.

The primary application of (S)-methanesulfonic acid 2triethylamine. The Boc-protected amine provides stability, while the mesylate group serves as a leaving group, enabling nucleophilic substitution reactions with various nucleophiles, such as amines, thiols, or cyanides, to form new carbon-nitrogen, carbon-sulfur, or carbon-carbon bonds. These transformations are critical for synthesizing chiral amines, amino acids, and other nitrogen-containing compounds used in pharmaceuticals. The (S)-configuration ensures that the resulting products are enantiopure, a requirement for many drugs where stereochemistry dictates biological activity. For example, this compound is used in the synthesis of protease inhibitors and other therapeutic agents, where precise control of molecular structure is essential.

In addition to pharmaceutical applications, (S)-methanesulfonic acid 2-Boc-amino-propyl ester is employed in academic research to explore new synthetic methodologies and reaction mechanisms. Its reactivity makes it an ideal substrate for studying nucleophilic substitution, stereoselective transformations, and the development of novel catalysts. The compound’s dual functionality—Boc protection and mesylate activation—allows chemists to manipulate molecular structures with high precision, contributing to advancements in synthetic efficiency.

The compound’s significance lies in its role as a key intermediate in the synthesis of complex chiral molecules. Its development reflects progress in protecting group chemistry, sulfonate ester reactivity, and asymmetric synthesis. By facilitating the production of enantiopure intermediates, it has advanced the creation of effective and selective pharmaceuticals, underscoring its importance in both industrial and research contexts.