tert-Butyl 1-piperazinecarboxylate
[CAS# 57260-71-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Piperazine
• Name: tert-Butyl 1-piperazinecarboxylate
• Synonyms: tert-Butyl tetrahydropyrazine-1(2H)-carboxylate; 1-N-Boc-Piperazine
• Molecular Formula: C₉H₁₈N₂O₂
• Molecular Weight: 186.25
• CAS Registry Number: 57260-71-6
• EC Number: 611-489-0
• SMILES: CC(C)(C)OC(=O)N1CCNCC1

Properties

• Density: 1.0$+/-$0.1 g/cm³ Calc.^*
• Melting point: 43 - 47 $degree$C (Expl.)
• Boiling point: 258.0$+/-$15.0 $degree$C 760 mmHg (Calc.)^*, 98 - 100 $degree$C (Expl.)
• Flash point: 109.8$+/-$20.4 $degree$C (Calc.)^*, 113 $degree$C (Expl.)
• Index of refraction: 1.467 (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
Serious eye damage	Eye Dam.	1	H318
Eye irritation	Eye Irrit.	2A	H319
Skin corrosion	Skin Corr.	1	H314
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

Discovery and Applications

tert-Butyl 1-piperazinecarboxylate is a heterocyclic compound in which a piperazine ring is N-protected with a tert-butoxycarbonyl (Boc) group. Piperazine derivatives are widely used in medicinal chemistry due to their basic nitrogen atoms, conformational flexibility, and ability to form hydrogen bonds, while the Boc protecting group stabilizes the nitrogen for selective synthetic transformations. The Boc group prevents undesired reactions at the piperazine nitrogen during multi-step syntheses, making this compound a versatile intermediate for the preparation of pharmaceuticals, agrochemicals, and functionalized heterocycles. Structurally, the molecule consists of a six-membered saturated piperazine ring containing two nitrogen atoms at opposite positions. One nitrogen is substituted with the Boc group, which consists of a tert-butyl moiety attached through a carbamate linkage (–NH–COO–tBu). This group is bulky and electron-withdrawing, providing steric hindrance and protecting the nitrogen from nucleophilic attack or alkylation during chemical reactions. The other nitrogen remains free or can later be functionalized to introduce substituents, allowing the creation of diverse derivatives. The synthesis of tert-butyl 1-piperazinecarboxylate typically involves reaction of piperazine with di-tert-butyl dicarbonate (Boc₂O) under basic conditions or with a suitable solvent such as dichloromethane. The Boc group selectively reacts with one nitrogen atom, leaving the other nitrogen available for further derivatization. Reaction conditions are optimized to prevent over-protection of both nitrogens, ensuring formation of the mono-Boc-protected intermediate. This approach provides a stable, isolable compound suitable for subsequent reactions in synthetic sequences. In medicinal chemistry, tert-butyl 1-piperazinecarboxylate is used extensively as a building block for drug discovery. The protected piperazine nitrogen allows selective functionalization of the free nitrogen to introduce pharmacophores, linkers, or solubilizing groups. The piperazine core contributes to aqueous solubility, hydrogen bonding, and metabolic stability, which are critical for the design of central nervous system agents, enzyme inhibitors, and receptor ligands. After desired functionalization, the Boc group can be removed under mild acidic conditions to release the secondary amine for final incorporation into the target molecule. Beyond pharmaceutical applications, this compound is valuable in organic synthesis as a scaffold for constructing heterocyclic libraries, conjugated molecules, and intermediates for chemical biology probes. The combination of a protected and a free nitrogen allows selective reactions such as acylation, sulfonylation, or alkylation, while maintaining the integrity of the heterocyclic core. The Boc group can also provide steric shielding in multi-step syntheses, facilitating regioselective or chemoselective transformations. Overall, tert-butyl 1-piperazinecarboxylate is a versatile and chemically stable intermediate featuring a Boc-protected piperazine ring. Its structural properties provide selective protection, synthetic flexibility, and suitability for medicinal chemistry and organic synthesis applications, making it a widely used scaffold for the development of functionalized heterocycles and bioactive compounds.

References

2025. Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging. EJNMMI Radiopharmacy and Chemistry.
DOI: 10.1186/s41181-025-00373-4

2025. Synthesis of new 4-(5-R-1-phenyl-1H-1,2,4-triazol-3-yl)benzamides. Russian Chemical Bulletin.
DOI: 10.1007/s11172-025-4639-x