Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate
[CAS# 889670-02-4]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate
• Synonyms: methyl 3-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• Protein Sequence: X
• Molecular Formula: C₉H₁₆INO₄
• Molecular Weight: 329.13
• CAS Registry Number: 889670-02-4
• SMILES: CC(C)(C)OC(=O)NC(CI)C(=O)OC

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Melting point: 50 - 52 ºC (Expl.)
• Boiling point: 356.5±32.0 ºC 760 mmHg (Calc.)^*
• Flash point: 169.4±25.1 ºC (Calc.)^*
• Index of refraction: 1.513 (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

Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate is a synthetic amino acid derivative that contains several key functional groups: an ester, a Boc-protected amine, and an iodine-substituted carbon. Its molecular structure is based on a modified alanine backbone, where the β-carbon is substituted with an iodine atom, and the α-amino group is protected with a tert-butoxycarbonyl (Boc) group. The esterification of the carboxylic acid forms the methyl ester, making the compound suitable for use in organic synthesis and peptide chemistry.

The compound is commonly prepared by iodination of Boc-protected serine or threonine derivatives. In one standard synthetic route, methyl 2-((tert-butoxycarbonyl)amino)-3-hydroxypropanoate is treated with a halogenating agent such as iodine and triphenylphosphine in the presence of an activating agent like imidazole or pyridine, resulting in substitution of the hydroxyl group by iodine via an Appel-type reaction. This yields the corresponding iodopropanoate with retention of the ester and Boc groups.

Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate is primarily used as a versatile intermediate in the synthesis of α-amino acid derivatives and noncanonical amino acids. The iodine atom at the β-position is a useful functional handle for further derivatization via cross-coupling reactions, particularly palladium-catalyzed transformations such as Suzuki-Miyaura, Sonogashira, or Heck reactions. These reactions enable the introduction of aryl, vinyl, alkynyl, or other groups to expand the diversity of the resulting compounds.

In peptide synthesis, the Boc group serves as a temporary protecting group for the amine functionality. It is stable under basic conditions but can be removed under acidic conditions such as treatment with trifluoroacetic acid, allowing for sequential coupling steps in solid-phase or solution-phase peptide synthesis. The methyl ester provides stability during coupling and can be hydrolyzed after assembly of the peptide to yield the free acid.

This compound has been employed in the development of unnatural amino acids for incorporation into peptide libraries or for modification of biologically active peptides. The ability to introduce functional groups at the β-position of amino acids is important for tuning the conformational, electronic, or binding properties of peptides and proteins.

In medicinal chemistry, derivatives of methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate have been used as intermediates in the synthesis of enzyme inhibitors and bioactive peptidomimetics. The iodine-substituted β-position allows for stereoselective modifications and enables the synthesis of conformationally restricted analogs. These modified amino acids can improve binding affinity, selectivity, or metabolic stability in drug candidates.

In summary, methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate is a synthetically valuable amino acid derivative used for constructing modified amino acids, peptides, and related bioactive molecules. Its reactivity, due to the presence of a Boc-protected amine, an ester group, and a reactive iodine substituent, makes it a flexible building block in modern organic and medicinal chemistry.