(R)-3-(Boc-Amino)piperidine
[CAS# 309956-78-3]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: (R)-3-(Boc-Amino)piperidine
• Synonyms: (R)-(+)-3-tert-Butoxycarbonylaminopiperidine
• Molecular Formula: C₁₀H₂₀N₂O₂
• Molecular Weight: 200.28
• CAS Registry Number: 309956-78-3
• EC Number: 685-989-2
• SMILES: CC(C)(C)OC(=O)N[C@@H]1CCCNC1

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Melting point: 116 - 121 °C (Expl.)
• Boiling point: 304.8±31.0 °C 760 mmHg (Calc.)^*
• Flash point: 138.2±24.8 °C (Calc.)^*
• Index of refraction: 1.48 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS09 Danger
• Risk Statements: H315-H318-H319-H335-H400
• Safety Statements: P261-P264-P264+P265-P271-P273-P280-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P332+P317-P337+P317-P362+P364-P391-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
Serious eye damage	Eye Dam.	1	H318
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Eye irritation	Eye Irrit.	2	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovery and Applications

(R)-3-(Boc-Amino)piperidine is a synthetically valuable, chiral, nitrogen-containing compound widely used as a building block in pharmaceutical and organic chemistry. Structurally, it consists of a six-membered piperidine ring bearing a single stereocenter at the 3-position. This stereocenter is substituted with a tert-butoxycarbonyl (Boc) protected amino group, which imparts both reactivity control and stability under standard reaction conditions.

The compound features an (R)-configuration, meaning the spatial orientation of the substituents around the chiral center adheres to the rectus (right-handed) convention. Chirality is critical in pharmaceutical development because biological systems are inherently chiral, and the (R)- and (S)-enantiomers of a molecule can exhibit dramatically different biological activities, including potency, toxicity, and metabolic pathways.

The Boc group is a common protecting group for amines, particularly in peptide synthesis and multi-step organic syntheses. It is base-stable and can be removed under acidic conditions, typically using trifluoroacetic acid (TFA), without affecting other acid-sensitive groups if chosen properly. This selective deprotection capability is essential in complex syntheses where orthogonal protection strategies are required.

(R)-3-(Boc-Amino)piperidine has been employed as a core scaffold or intermediate in the synthesis of various drug-like molecules, including central nervous system agents, antiviral compounds, and kinase inhibitors. The presence of the piperidine ring contributes to the compound’s basicity and conformational flexibility, characteristics that often improve binding affinity to biological targets. Moreover, substitution at the 3-position of the piperidine ring, especially in a stereodefined manner, has been shown to influence the shape and electronic properties of lead compounds, allowing for fine-tuning of pharmacological activity.

In medicinal chemistry, this compound serves as a precursor for more elaborated heterocyclic systems, including fused bicyclic amines or constrained analogs of natural products. It is often used in the synthesis of substituted piperidine-based pharmacophores, which are present in numerous drug classes such as antihistamines, antipsychotics, analgesics, and antiretrovirals.

During synthesis, the Boc-protected amine ensures that the nitrogen does not participate in unwanted side reactions. Once the core structure is assembled or functionalized, deprotection yields the free amine, which can undergo further derivatization such as alkylation, acylation, sulfonation, or reductive amination.

Due to its versatility, (R)-3-(Boc-Amino)piperidine is available commercially and is used in both academic and industrial laboratories. Its enantiomeric purity is particularly important in the development of single-enantiomer drugs, which are now preferred in regulatory approval processes due to their predictable pharmacokinetic and pharmacodynamic profiles.

Overall, (R)-3-(Boc-Amino)piperidine exemplifies how the incorporation of chirality, strategic protection, and a flexible nitrogen-containing ring system can result in a highly useful intermediate for the construction of biologically active molecules across a wide range of therapeutic areas.

References

2014. Linagliptin. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-12-0077

2018. Synthesis of GDC-0575. Synfacts, 14(6).
DOI: 10.1055/s-0037-1609521

2021. Convenient Synthesis of (R)-3-[(tert-Butoxycarbonyl)amino]piperidine and (R)-3-[(tert-Butoxycarbonyl)amino]azepane. Synthesis, 53(21).
DOI: 10.1055/a-1526-7657