1. Product Overview
N-Boc-3-methyl-4-piperidinecarboxylic Acid (CAS 512822-50-3) is a Boc-protected piperidine derivative bearing a 3-methyl substituent and a 4-position carboxylic acid group. The molecule features orthogonal reactivity: the carboxylic acid can undergo standard amide/ester coupling, while the tertiary amine remains protected by the acid-labile tert‑butyloxycarbonyl (Boc) group, which can be cleanly removed under mild acidic conditions (e.g., TFA or HCl in dioxane) without affecting the carboxyl moiety. This compound is a key chiral/non-chiral building block in medicinal chemistry for assembling substituted piperidine scaffolds found in CNS-active agents, 5‑HT₄ receptor agonist candidates, and other GPCR-targeted drug leads.
2. Key Features and Benefits
• Orthogonal Protection Strategy: Boc group allows selective deprotection independent of the carboxylic acid, enabling sequential, chemo-selective synthetic steps.
• Conformational Influence by 3‑Methyl Group: The C‑3 methyl substituent alters the piperidine ring conformation, pKa (~4.57), and calculated LogP (~1.6) relative to the des‑methyl analog, facilitating structure–activity relationship (SAR) optimization in drug design.
• High Purity & Reproducibility: Supplied ≥98% (HPLC/GC), with full CoA including ¹H NMR verification, minimizing batch-to-batch variability in multi-step synthesis.
• Versatile Coupling Handle: Carboxylic acid activates readily with EDC/HOBt, DCC, or HATU for peptide-like coupling or esterification in library synthesis.
• Stable Solid Form: White to off-white crystalline solid, low hygroscopicity, good shelf life under recommended storage.
3. Major Applications
• Medicinal Chemistry / Drug Discovery: Used in the synthesis of indazole and pyrrolopyridine derivatives as 5‑HT₄ receptor agonists for Alzheimer's disease research.
• Piperidine-Based API Intermediates: Core scaffold for CNS drugs, antipsychotics, and anti‑cancer candidates containing N‑heterocyclic motifs.
• Diversity-Oriented Synthesis (DOS): Employed in building piperidine-containing fragment libraries for high-throughput screening.
• Peptidomimetics: The Boc-piperidine-4-carboxylic acid framework is a common β‑turn mimetic or proline surrogate in peptide-based drug design.
4. Technical Specifications
5. Storage and Handling
• Storage: Keep the sealed container at 2–8 °C in a dry, dark place. For long-term storage (>12 months), a desiccator is recommended. The Boc group is stable at this temperature but may hydrolyze slowly under prolonged exposure to high humidity or strong acid/base.
• Handling: Allow the vial to warm to ambient temperature before opening to prevent moisture condensation. Dissolve in anhydrous organic solvent (DMSO, MeOH, DCM) as required. The free acid may require gentle warming or addition of a minimal amount of base (e.g., NaHCO₃ sat. aq.) for complete dissolution in polar aprotic solvents.
• Boc Deprotection: Treat with 4 M HCl in dioxane (or TFA/DCM, 1:1 v/v) at RT for 30–60 min; evaporate, neutralize if needed, to obtain the corresponding piperidine hydrochloride salt ready for further N‑alkylation or acylation.
6. Safety Summary
• GHS Classification: GHS07 – Warning
• Hazard Statements: H315 (Causes skin irritation); H319 (Causes serious eye irritation); H335 (May cause respiratory irritation).
• Precautionary Statements: P261 (Avoid breathing dust/mist); P264 (Wash after handling); P280 (Wear protective gloves/eye protection); P302+P352 (If on skin: wash with soap and water); P305+P351+P338 (If in eyes: rinse with water for several minutes; remove contact lenses if present); P337+P313 (If eye irritation persists: seek medical advice).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use.
