N-BOC-4-Hydroxypiperidine
[CAS# 109384-19-2]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: N-BOC-4-Hydroxypiperidine
• Synonyms: N-(tert-Butoxycarbonyl)-4-hydroxypiperidine
• Molecular Formula: C₁₀H₁₉NO₃
• Molecular Weight: 201.26
• CAS Registry Number: 109384-19-2
• EC Number: 600-916-6
• SMILES: CC(C)(C)OC(=O)N1CCC(CC1)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Melting point: 61 - 65 °C (Expl.)
• Boiling point: 292.3±33.0 °C 760 mmHg (Calc.)^*
• Flash point: 130.6±25.4 °C (Calc.)^*
• Index of refraction: 1.496 (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

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

N-BOC-4-Hydroxypiperidine is a Boc-protected 4-hydroxypiperidine featuring a piperidine ring with a tert-butoxycarbonyl (Boc) group on the nitrogen and a hydroxyl moiety at the 4-position. Its molecular formula is C₁₀H₁₉NO₃, and it typically appears as a white or off-white crystalline powder, highly soluble in organic solvents such as methanol, ethanol, dichloromethane, and chloroform. The Boc protection enhances its chemical stability and handling.

This compound is primarily employed as a versatile building block in organic synthesis, especially in pharmaceutical research and development. The Boc group serves as a temporary protective group for the amine, allowing selective reactions elsewhere. This facilitates multi-step syntheses of piperidine-containing bioactive molecules while maintaining control over functional group reactivity. Upon completion of downstream transformations, the Boc group can be removed under mild acidic conditions to release the free amine.

In medicinal chemistry, N-BOC-4-Hydroxypiperidine is used in the synthesis of neurologically active agents, peptide analogs, and small-molecule drugs. It functions effectively in Mitsunobu etherification to create N-heterocyclic alkyl ethers. It also serves in the preparation of BTK inhibitor intermediates, and has been implicated in the assembly of compounds with activity at muscarinic receptors and mineralocorticoid receptors. The combination of the hydroxyl group and Boc protection provides branching points for further modification, including esterification, ether formation, and conjugation with other pharmacophores.

The synthetic route often involves the reaction of 4-hydroxypiperidine with di-tert-butyl dicarbonate (Boc₂O) in the presence of base such as sodium bicarbonate, typically in dichloromethane or aqueous-organic mixtures at ambient temperature. The reaction proceeds with high yield and furnished N-BOC-4-Hydroxypiperidine as a crystalline solid. For industrial-scale production, a two-step approach starting from 4-piperidone includes reduction to 4-hydroxypiperidine followed by Boc protection. This process yields high purity product suitable as a pharmaceutical intermediate.

As a reagent, N-BOC-4-Hydroxypiperidine is commercially available in high-purity grades (≥97 %), and stored at cool conditions. It is classified as an irritant, requiring standard protective equipment to avoid skin, eye, and respiratory exposure. Handling should be conducted in well-ventilated areas.

In summary, N-BOC-4-Hydroxypiperidine is an important Boc-protected amino alcohol used extensively in pharmaceutical synthesis. Its dual functionality enables selective transformations, while its relatively simple preparation and commercial availability make it a staple intermediate for piperidine-based drug research.

References

2024. Scalable deoxygenative alkynylation of alcohols via flow photochemistry. Communications Chemistry, 7(1).
DOI: 10.1038/s42004-024-01363-4

2022. Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1).
DOI: 10.1080/14756366.2022.2070909

2018. HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis. Experimental & Molecular Medicine, 50(9).
DOI: 10.1038/s12276-018-0152-8