Tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate
[CAS# 180532-52-9]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: Tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate
• Molecular Formula: C₁₁H₂₁NO₃
• Molecular Weight: 215.29
• CAS Registry Number: 180532-52-9
• SMILES: CC(C)(C)OC(=O)CC1(CCNCC1)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 302.6±17.0 °C 760 mmHg (Calc.)^*
• Flash point: 136.8±20.9 °C (Calc.)^*
• Index of refraction: 1.473 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319
• Safety Statements: P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Discovery and Applications

Tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate is an organic compound composed of a substituted piperidine ring bearing a hydroxyl group at the 4-position, and a tert-butyl ester of acetic acid attached at the same carbon. This structure combines a six-membered saturated heterocycle with a sterically protected carboxylic acid derivative, offering functional flexibility for synthetic applications.

The piperidine ring is a common motif in medicinal chemistry, often valued for its conformational rigidity and ability to modulate bioavailability and binding affinity in pharmaceutical candidates. In this compound, the 4-position is doubly substituted—bearing both a hydroxyl group and a side chain leading to the ester. The presence of the tert-butyl ester protects the carboxylic acid from premature hydrolysis during synthetic transformations, allowing for downstream reactions without loss of the acid functionality.

Synthesis of tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate generally begins with the functionalization of 4-hydroxypiperidine or protected piperidinone derivatives. Alkylation of the 4-position with tert-butyl bromoacetate or similar esters under basic conditions leads to the formation of the ester-substituted product. The reaction typically proceeds under mild conditions and is scalable for both research and preparative purposes.

This compound serves as a key intermediate in the synthesis of drug-like molecules, particularly those targeting central nervous system receptors or enzymes. The hydroxyl group at the 4-position provides a handle for further functionalization, including etherification, acylation, or conversion to leaving groups for substitution reactions. The tert-butyl ester can be removed under acidic conditions (e.g., trifluoroacetic acid) to reveal the corresponding carboxylic acid for subsequent amide coupling or salt formation.

Compounds bearing similar piperidine-based side chains have appeared in small-molecule inhibitors of proteases, GPCR ligands, and enzyme cofactors. The balance of hydrophilicity from the hydroxyl and carboxylic acid functionalities and the lipophilicity imparted by the tert-butyl group makes this compound suitable for optimizing pharmacokinetic properties in lead development programs.

In conclusion, tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate is a synthetically useful intermediate that merges a functionalized piperidine core with a protected carboxylic acid moiety. Its modular design allows for diverse chemical modifications, making it a valuable building block in medicinal chemistry and drug discovery research.