Chemical Identity and Structure

2-(1-Boc-piperazin-4-yl)-acetic acid 2H2O (Aladdin Scientific SKU: B179017) consists of a six-membered piperazine ring in which the N-1 nitrogen bears a tert-butoxycarbonyl (Boc) protecting group and the N-4 nitrogen carries an acetic acid (–CH₂COOH) pendant arm. The compound is isolated as the dihydrate salt, meaning two water molecules are incorporated per formula unit of the organic core.

The dual functionality of this molecule — a Boc-protected amine on one end and a free carboxylic acid on the other — makes it a bifunctional linker ideal for sequential coupling chemistry. The Boc group selectively masks the N-1 amine under mild conditions, leaving the carboxylic acid available for amide bond formation, esterification, or other acylation reactions without additional protecting-group manipulations.

Key structural features:

• Piperazine scaffold: conformationally flexible, water-solubilizing ring system widely represented in approved drugs
• N-Boc group: acid-labile orthogonal protector removed by trifluoroacetic acid (TFA) or HCl in dioxane
• Acetic acid arm: directly available for coupling reactions under standard DIC/HATU/EDC activation protocols
• Dihydrate form: stable crystalline solid; molecular weight calculation must account for 2 × 18.015 g/mol water

Recommended Handling and Storage Procedures

Proper handling of 2-(1-Boc-piperazin-4-yl)-acetic acid 2H2O preserves chemical integrity, prevents moisture uptake beyond the defined dihydrate state, and ensures reproducible results in downstream synthetic steps. Follow the procedures below:

Personal Protective Equipment (PPE)

• Wear nitrile gloves, safety spectacles, and a laboratory coat at all times when handling the solid or its solutions.
• Work in a well-ventilated area or fume hood, particularly when preparing concentrated solutions.

Storage Conditions

• Store the sealed container at 2–8 °C (refrigerator) or at room temperature in a cool, dry location away from direct light, moisture, and incompatible reagents such as strong acids or oxidising agents.
• The dihydrate form is stable under normal laboratory storage; avoid desiccant conditions that may cause partial dehydration and alter the effective molarity of weighed portions.
• Always re-seal the container tightly under inert atmosphere (nitrogen or argon) after each use to prevent adventitious moisture absorption.

Dissolution and Solution Preparation

• The compound is soluble in polar aprotic solvents (DMF, DMSO) and aqueous buffers at appropriate pH; solubility in pure water is limited by the zwitterionic nature of the molecule at neutral pH.
• When preparing stock solutions, account for the dihydrate molecular weight in stoichiometric calculations.
• Freshly prepared solutions are recommended; if storing dissolved material, use –20 °C and avoid repeated freeze–thaw cycles.

Waste Disposal

• Dispose of waste in accordance with local institutional and regulatory guidelines for organic chemical waste.

Synthetic Applications and Reaction Protocols

2-(1-Boc-piperazin-4-yl)-acetic acid 2H2O serves as a core building block in medicinal chemistry programmes targeting kinases, GPCRs, ion channels, and other therapeutic targets where a piperazine-containing pharmacophore is desired. The compound enables modular, orthogonal synthesis strategies:

Amide Bond Formation (Carboxylic Acid Utilisation)

The free carboxylic acid at N-4 can be activated using standard coupling reagents and reacted with primary or secondary amines to install amide bonds:

• HATU/DIPEA in DMF: Most efficient for hindered amines; use 1.1–1.5 equivalents of HATU and 3 equivalents of DIPEA relative to the acid. React at room temperature for 1–4 hours.
• EDC·HCl / HOBt in DMF or CH₂Cl₂: Suitable for less hindered amine coupling partners; cost-effective for scale-up.
• DIC / Oxyma in DMF: Low-epimerisation protocol compatible with solid-phase peptide synthesis (SPPS) workflows.

Boc Deprotection Protocol

After utilising the carboxylic acid in a coupling step, the Boc group can be selectively removed to liberate the secondary piperazine amine for further functionalisation:

• TFA / CH₂Cl₂ (20–50% v/v), 0 °C to RT, 30–60 min: Standard deprotection; neutralise TFA salt with excess DIPEA or aqueous base before subsequent reactions.
• 4 M HCl in dioxane, RT, 1–2 h: Delivers HCl salt of the free amine; useful when TFA-sensitive functionality is present elsewhere in the molecule.

Use in Fragment-Based Drug Discovery (FBDD)

The compound functions as a fragment extender or linker unit, connecting a warhead fragment to a recognition element via the flexible –CH₂– spacer and the piperazine ring. The piperazine nitrogen, once deprotected, can undergo reductive amination, sulfonylation, or acylation to generate diverse compound libraries.

Solid-Phase Synthesis Compatibility

The carboxylic acid can be loaded directly onto Rink amide or Wang resin using standard resin-loading protocols. Subsequent on-resin Boc deprotection and diversification steps are compatible with Fmoc SPPS workflows after appropriate protecting-group strategy adjustment.

Quality, Purity, and Analytical Verification

For reliable downstream synthesis and biological evaluation, researchers should verify the identity and purity of 2-(1-Boc-piperazin-4-yl)-acetic acid 2H2O upon receipt and before use. Aladdin Scientific provides analytical data with each lot; users are encouraged to perform in-house confirmation using the following techniques:

¹H NMR Spectroscopy

Record spectrum in D₂O or DMSO-d₆. Key expected resonances include: δ ~1.40 ppm (s, 9H, Boc tert-butyl), δ ~2.4–2.6 ppm (m, 4H, piperazine CH₂ adjacent to N-4), δ ~3.0–3.4 ppm (m, 4H, piperazine CH₂ adjacent to N-1), and δ ~3.1 ppm (s, 2H, –CH₂COOH). The dihydrate water signal appears at δ ~3.3 ppm in DMSO-d₆.

LC-MS / HPLC

Use a C18 reverse-phase column with 0.1% formic acid in water / acetonitrile gradient. Confirm molecular ion [M+H]⁺ consistent with the free-acid dihydrate molecular formula. Purity ≥95% by UV at 214 nm is acceptable for most synthetic applications; ≥98% is recommended for biological assays.

Karl Fischer Titration

To verify the dihydrate water content precisely, Karl Fischer coulometric titration is recommended. Theoretical water content for the dihydrate should be confirmed against the lot certificate of analysis (CoA).

Melting Point

Comparison against literature or CoA values provides a quick purity indicator for the crystalline solid.

Storage Integrity Check

If the compound has been stored for an extended period, re-check purity by HPLC before use, as partial hydrolysis or dehydration of the dihydrate may alter effective concentration in weighed samples.

Regulatory, Safety, and Procurement Information

Researchers and procurement officers should be aware of the following considerations when ordering and using 2-(1-Boc-piperazin-4-yl)-acetic acid 2H2O (B179017) from Aladdin Scientific:

Safety Classification

This compound is an organic solid of moderate complexity. It is not classified as a controlled substance, explosive, or acutely toxic material under standard laboratory chemical classifications; however, always consult the Safety Data Sheet (SDS) provided with the product for the most current GHS hazard classification, first-aid measures, and spill-handling procedures. Standard laboratory precautions apply.

Regulatory Status

The compound is intended for research use only (RUO) and is not approved for use in clinical diagnostics, therapeutic applications, or food/feed. End users are responsible for compliance with all applicable local, national, and international regulations.

Ordering and Packaging

Product B179017 is available through Aladdin Scientific's standard ordering channels. Contact your regional Aladdin Scientific representative or place orders via the official website. Packaging sizes and lot-specific CoA documents are available upon request. Bulk and custom quantities may be arranged through the technical sales team.

Shipping and Stability During Transit

The dihydrate solid is stable at ambient temperature during short-term transit; refrigerated shipping is recommended for orders involving warm climates or extended delivery times to maintain optimal product quality. Upon receipt, inspect the container for integrity and compare the lot number against the accompanying CoA.

Returns and Quality Issues

Should the product not meet the stated specifications, contact Aladdin Scientific customer service within the return window specified on your order confirmation. Provide the lot number, CoA, and analytical data supporting the quality concern to expedite resolution.