2-Cyclopropylpiperidine hydrochloride - ≥97% , CAS No.1894128-11-0

CAS: 1894128-11-0 Cat. No.: C1306372 Formula: C₈H₁₆ClN Peso molecolare: 161.67

GRADE & PURITY ≥97%

Storage

Room temperature

Shipped In

Normal

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Purezza

≥97%

Nomi e identificatori

Sorrisi canonici

C1CCNC(C1)C2CC2.Cl

IUPAC Name

2-cyclopropylpiperidine;hydrochloride

InChIKey

CPNCCPDSVAKLSZ-UHFFFAOYSA-N

INCHI

1S/C8H15N.ClH/c1-2-6-9-8(3-1)7-4-5-7;/h7-9H,1-6H2;1H

Peso molecolare

161.67

Proprietà chimiche e fisiche

• Peso molecolare: 161.670 g/mol
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 161.097 Da
• Monoisotopic Mass: 161.097 Da
• Topological Polar Surface Area: 12.000 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 96.700
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 2

XLogP3

Application Protocols

Not applicable for assay protocols such as WB, IHC, IF, or FC. This product is a synthetic intermediate. For practical laboratory use, see the Reaction Conditions and Synthetic Utility sections for general procedures (e.g., free-basing, amide coupling, reductive amination). For any analytical characterization, standard small-molecule methods (1H/13C NMR, LC-MS, HPLC purity) are recommended.

Biological Roles

This product is intended for laboratory research and synthetic use. No biological activity data are provided for this specific item.

• General context (literature-based; not specific to this item)

  • Piperidine rings are common motifs in natural products and medicinal chemistry, often serving as basic, solubilizing elements in ligands for receptors, transporters, and enzymes.
  • The cyclopropyl group can act as a metabolically robust, conformationally constraining substituent that modulates physicochemical properties (lipophilicity, steric profile) without large increases in molecular weight.
  • As a small aliphatic amine salt, the compound may be used as a building block to access bioactive analogs for SAR exploration; however, the compound itself is not claimed to possess inherent biological function as supplied here.

• Research use note (Product Data)

  • For research use only. Not for human or veterinary use, clinical diagnosis, or therapeutic applications.

Buffer Applications

Not typically used as a buffering reagent. As an amine hydrochloride, it can influence solution pH by acid–base equilibria, but defined buffering capacity and pKa specifications for a buffer system are not provided for this item. For buffer preparation and pH control, select dedicated buffering agents (e.g., phosphate, Tris, HEPES) and refer to their specific pH ranges and recipes.

Green Alternatives

• Solvent and reagent choices can significantly improve the sustainability profile of transformations using 2-cyclopropylpiperidine hydrochloride. The following suggestions are general/literature-based and should be validated for your specific chemistry.

• Greener solvent substitutions (general)

  • Replace DMF/DMAc with safer polar aprotics such as Cyrene, dimethyl carbonate (where feasible), or propylene carbonate for some coupling and substitution reactions.
  • Use ethanol or isopropanol instead of methanol or chlorinated solvents for reductive amination and simple salt manipulations when compatible.
  • Favor 2-MeTHF or CPME over THF/MTBE for extractions of the free base (improved safety, lower peroxide risk vs. Et2O; note still flammable).

• Greener coupling strategies

  • Employ aqueous micellar catalysis (e.g., TPGS-750-M) for amide bond formations or SNAr where possible, reducing organic solvent volumes.
  • Consider enzymatic amide formation (acyl transferases or peptiligases) for selected substrates under mild, aqueous conditions.

• Reductive amination

  • Use hydrogenation (H2, Pd/C) or transfer hydrogenation (HCO2NH4, Pd/C) as alternatives to NaBH3CN/NaBH(OAc)3 to avoid cyanide- or borane-containing waste, when chemoselectivity allows.

• Comparison highlights (general)

  • DMF vs. Cyrene: Cyrene offers better EHS profile; viscosity and reactivity differences may require temperature/stoichiometry adjustments.
  • DCM vs. EtOAc/2-MeTHF: EtOAc and 2-MeTHF reduce chlorinated waste; check solubility and reaction rates.

Balance green choices with safety, throughput, and product quality; confirm by small-scale trials.

Pharmaceutical Uses

• Item-specific (Product Data)

  • No pharmacopeial status, excipient role, or GMP grade is specified for this item; refer to CoA/Spec Sheet. Supplied for research use only.

• General context (non-clinical; for process and discovery chemistry)

  • Role as an intermediate: 2-cyclopropylpiperidine hydrochloride can serve as a key amine building block in the synthesis of candidate APIs during lead optimization, typically converted to amides, ureas, sulfonamides, or N-alkyl derivatives.
  • Salt handling in process development: Hydrochloride salts are often preferred for handling and crystallinity. Counterion exchange (e.g., to mesylate, tosylate, citrate) may be used to optimize solid-state properties of intermediates.
  • Analytical controls: Impurity profiling (residual solvents, related substances), salt stoichiometry verification, and polymorph/solvate screening are standard considerations in process routes employing amine salts.

No therapeutic claims are made for this product. Any application toward drug substance manufacture requires appropriate regulatory and quality assessment.

Physical Properties

• Item-specific (Product Data)

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed values (informational; verify experimentally for this specific item)

  • Empirical formula (HCl salt, literature-based): C8H17NCl (derived from 2-cyclopropylpiperidine·HCl).
  • Formula weight (calculated): ~162.68 g/mol.
  • Physical state tendency: amine hydrochloride salts are typically crystalline, non-volatile solids with moderate hygroscopicity (general behavior; not item-specific).
  • Solubility (general): amine hydrochlorides are usually freely soluble in water and polar protic solvents (MeOH, EtOH) and variably soluble in polar aprotic media (DMF, DMSO, acetonitrile). Limited solubility is typical in nonpolar solvents (hexanes, toluene). Actual solubility must be determined for this lot.
  • pKa (related system, literature): piperidinium conjugate acid pKa ≈ 11.1–11.6 (free base in water, 25 °C). Substitution at C-2 can slightly modulate basicity; use as a qualitative guide only.
  • Partitioning: as a hydrochloride salt, the compound exists predominantly as a charged species in neutral water, favoring aqueous over organic phases; conversion to the free base increases lipophilicity (general behavior).

• Not provided for this item (consult CoA/SDS for authoritative values)

  • Melting point, boiling point, density, refractive index, UV cutoff, residual solvents, water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• Item-specific (Product Data)

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/Inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

• Guidance on interpreting grades (general; for context)

  • Research grade: Suitable for most synthetic and discovery workflows. Impurity profiles may not be fully constrained for trace metals or low-level volatiles.
  • ≥98–99% purity (when specified): Typically acceptable for medicinal chemistry SAR, parallel synthesis, and library production. For stereochemical applications, ensure enantiomeric/diastereomeric ratio specifications are stated if relevant.
  • HPLC grade (for solvents) or LC-MS grade (for analytes): Implies low UV background and minimal non-volatile residues; not applicable unless explicitly specified for this item.

• What to verify on receipt

  • Identity: Confirm by NMR and HRMS; for salts, verify the counterion and stoichiometry (1:1 HCl unless specified otherwise) via titration or ion chromatography.
  • Purity: Assess by HPLC/UPLC and qNMR. Check for salt form homogeneity and absence of free base.
  • Water content: Karl Fischer where relevant; many amine salts are mildly hygroscopic. Not specified for this item; refer to CoA/Spec Sheet.
  • Residual solvents/metals: Not specified for this item; refer to CoA/Spec Sheet.

Contact us for alternate grades (free base vs. HCl salt, enantiopure variants, or custom specifications) if your workflow requires them.

Reaction and Applications

As a saturated secondary amine (provided as the HCl salt), 2-cyclopropylpiperidine is a versatile synthon for discovery chemistry and heterocycle modification.

• Representative application families (general/literature guidance)

  • Amide formation: Coupling with carboxylic acids (e.g., HATU/HBTU/EDC or acid chlorides/anhydrides) to furnish tertiary amides bearing a constrained cyclopropyl–piperidine motif.
  • Sulfonamide/urea/carbamate synthesis: Reaction with sulfonyl chlorides, isocyanates, or carbonates; Boc protection then downstream transformations when chemoselectivity is needed.
  • Reductive amination: Condensation with aldehydes/ketones followed by reduction (NaBH3CN, NaBH(OAc)3, or catalytic hydrogenation), enabling N-alkyl diversification.
  • N-arylation/SNAr: Coupling to electron-deficient aryl halides/triflates under Pd catalysis (Buchwald–Hartwig) or SNAr on nitro/fluoro-activated arenes.
  • Quaternization/salt switching: Alkylation to quaternary ammonium salts; counterion exchange to modulate solubility/crystallinity.

• Medicinal chemistry context (general)

  • The 2-substituted piperidine scaffold is prevalent in probe and lead-like libraries. The cyclopropyl substituent imparts rigidity and lipophilicity while minimizing steric bulk, often used to modulate metabolic soft spots and influence basicity (qualitative trends).

• Practical tips

  • Free-basing: Neutralize the HCl salt with aqueous base (NaHCO3/Na2CO3) and extract into an organic solvent to access the free amine prior to moisture-sensitive couplings.
  • Protection: Boc protection (Boc2O, base) or Cbz (Cbz–Cl) helps manage selectivity; remove under standard acidic (Boc) or hydrogenolysis (Cbz) conditions.
  • Stereochemical considerations: C-2 substitution creates a stereocenter; racemic mixtures are common unless an enantioenriched material is specified. Plan for chiral resolution or asymmetric synthesis if stereochemistry is critical.

Reaction Conditions

The following conditions are general literature guidance for secondary amines of the piperidine class and should be optimized for your substrate set. They are not item-specific specifications.

• Amide coupling

  • Typical: Carboxylic acid (1.0–1.2 eq), HATU or EDCI (1.1–1.5 eq), DIPEA (2–4 eq), solvent DMF or DCM, 0–25 °C, 1–16 h. Isolated yields commonly 70–95% for unhindered partners.
  • Acid chloride route: Acid chloride (1.1 eq), base (2–3 eq; triethylamine or DIPEA), DCM/THF, 0 °C to rt, 0.5–2 h.

• Reductive amination

  • Carbonyl (1.0–1.5 eq) with the free base, NaBH(OAc)3 (2–3 eq) in DCE/MeCN/MeOH, 0–25 °C, 2–16 h. Alternatively, H2 (1–5 bar), Pd/C (5–10 wt%), MeOH/EtOH, rt–40 °C.

• N-arylation (Buchwald–Hartwig)

  • Aryl bromide/chloride (1.0 eq), Pd2(dba)3 or Pd(OAc)2 (1–3 mol%), BINAP/XPhos/BrettPhos (2–6 mol%), NaOtBu or Cs2CO3 (2–3 eq), toluene/dioxane, 60–110 °C, 4–24 h.

• SNAr

  • Activated aryl fluoride/nitro arene (1.0 eq), base K2CO3/Cs2CO3 (2–3 eq), DMF/DMAc, 50–100 °C, 4–24 h.

• Protection (Boc)

  • Boc2O (1.1–1.5 eq), base (NaHCO3/triethylamine), THF/MeOH or dioxane/H2O, 0–25 °C, 1–4 h.

• Free-basing the HCl salt

  • Dissolve in water or MeOH/H2O, add NaHCO3 or Na2CO3 to pH > 10, extract with EtOAc/2-MeTHF, dry and concentrate. Use immediately or store under inert atmosphere at low temperature to minimize volatility/oxidation of the free base.

Always conduct small-scale trials and analytical monitoring (TLC, LC-MS, in-process NMR) to optimize equivalents and temperatures for your system.

Safety and Handling

• Item-specific (Product Data)

  • GHS classification, signal word, H-statements, pictograms: Not specified for this item; refer to SDS.
  • Storage conditions: Room temperature (Product Data). Store in original, tightly closed container.
  • Shipping: Shipped under normal conditions (Product Data).

• General safety guidance for amine hydrochloride salts (not item-specific; consult SDS for definitive information)

  • Hazards: May cause skin/eye irritation and respiratory tract irritation. Dust may be harmful if inhaled. Avoid creating dust/aerosols.
  • PPE: Use lab coat, safety glasses or face shield, and suitable chemical-resistant gloves (e.g., nitrile). Employ local exhaust ventilation or work in a fume hood.
  • Handling: Minimize moisture exposure; many amine HCl salts are mildly hygroscopic. Avoid contact with bases and strong oxidizing agents. Prevent contact with strong bases that can liberate the free amine and HCl.
  • First aid (overview): If inhaled, move to fresh air; seek medical attention if symptoms occur. In case of skin contact, wash with soap and water. For eye contact, rinse cautiously with water for several minutes; remove contact lenses if present and easy; seek medical advice. If swallowed, rinse mouth; do not induce vomiting; obtain medical attention.
  • Fire safety: Organic solids can burn; use water spray, dry chemical, CO2, or foam. Combustion may produce HCl, NOx, and CO/CO2.
  • Spill response: Avoid dust, collect mechanically or dampen and absorb; dispose of according to local regulations.

Always consult the product-specific SDS for authoritative hazard information and emergency procedures.

Solvent Selection

This compound is supplied as a protonated amine (hydrochloride salt), which strongly influences solubility and phase behavior.

• General polarity/miscibility (literature-based trends; not item-specific specifications)

  • Water and polar protic solvents (MeOH, EtOH): Typically very good solubility for amine HCl salts; useful for salt-to-free-base conversions or direct use in aqueous-phase couplings.
  • Polar aprotic solvents (DMSO, DMF, NMP): Usually dissolve amine salts well; beneficial for peptide coupling, urea/sulfonamide formations, and SNAr reactions.
  • Moderately polar organics (acetonitrile, isopropanol): Often adequate; check solubility empirically.
  • Nonpolar solvents (toluene, MTBE, hexanes): Limited solubility expected for the salt; convert to free base for use in these media.

• Practical selection tips

  • For amide couplings: DMF, NMP, or DCM with in situ base (DIPEA) after pre-neutralization of the salt.
  • For reductive amination: MeOH/EtOH or MeCN with a base to liberate the free amine; DMSO or DMF for challenging substrates.
  • For SNAr/arylation: DMAc/DMF with inorganic base (K2CO3/Cs2CO3) after free-basing.

• Quick comparison (general)

  • DMSO: Maximum solubilizing power; higher boiling, challenging workup.
  • DMF: Excellent balance of solubility and handling; regulated in some jurisdictions.
  • MeOH/EtOH: Green(er), easy removal; may require base to free the amine from its HCl salt.

Always confirm actual solubility for this specific lot and application.

Storage and Reconstitution

• Item-specific (Product Data)

  • Storage conditions: Room temperature.
  • Shipped in: Normal conditions.

• General handling guidance for amine hydrochloride salts (not item-specific)

  • Container: Store in a tightly closed, moisture-protected container. Many amine HCl salts are mildly hygroscopic; minimize exposure to ambient humidity.
  • Light/air: Protect from prolonged exposure to air to avoid moisture uptake; light sensitivity is generally low for saturated amines but store away from direct light as good practice.
  • Inert atmosphere: Not strictly required for most salts, but beneficial for long-term storage once opened.

• Reconstitution and use

  • Solubilization: Begin with water, methanol, ethanol, or DMSO depending on the intended application. Verify solubility on a small scale for this specific lot.
  • Free-basing (if required): Neutralize an aqueous solution/suspension with NaHCO3 or Na2CO3 to liberate the free amine; extract into an organic solvent (e.g., EtOAc or 2-MeTHF), dry, and use promptly.
  • Freeze–thaw: Not typically applicable to solids; if preparing stock solutions, aliquot and store at appropriate temperature to avoid repeated freeze–thaw cycles.

For definitive storage limits, stability, and any specific impurity controls, refer to the product’s CoA and SDS.

Structure and Identity

A saturated nitrogen heterocycle building block supplied as the hydrochloride salt of a 2-substituted piperidine, suitable for use in fragment elaboration and amide/sulfonamide synthesis.

• Item-specific (Product Data)

  • Product name: 2-Cyclopropylpiperidine hydrochloride
  • CAS: 1894128-11-0
  • CID: 115012710
  • InChIKey: 50307 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature identity (general chemistry information)

  • Expected neutral free-base core: a piperidine ring (six-membered saturated N-heterocycle) bearing a cyclopropyl substituent at C-2 (adjacent to the ring nitrogen), with the commercial material present as the protonated ammonium chloride salt.
  • Likely empirical formula for the HCl salt: C8H17NCl (derived from 2-cyclopropylpiperidine·HCl; literature rationale). This is a computed/literature value, not an item-specific specification.
  • Approximate formula weight (literature calculation): ~162.68 g/mol for the HCl salt (C8H17NCl). This is a computed value; verify on the item’s CoA.

• Structural features (general description)

  • Ring systems: one saturated six-membered ring (piperidine), one cyclopropyl ring substituent.
  • Functional groups: secondary ammonium (as hydrochloride), aliphatic carbocycles.
  • Stereochemistry: If the cyclopropyl is attached at C-2, the carbon is stereogenic when N is part of the ring; commercial material is commonly racemic unless otherwise specified (no stereochemical specification provided for this item). 2D depiction would show piperidine chair with N–H+ (as salt) and a cyclopropyl substituent at the α-carbon to nitrogen; chloride as counterion.

Synthetic Utility

2-Cyclopropylpiperidine hydrochloride is a conformationally biased, basic amine building block. The C-2 stereogenic center (when defined) and the compact cyclopropyl substituent provide handles for tuning potency and ADME in analog series.

• Functional group reactivity (general)

  • Nucleophilic amine center: engages in acylation (amides, carbamates), sulfonylation, and alkylation.
  • Reductive amination partner: forms tertiary amines with carbonyl compounds under mild conditions.
  • Cross-coupling partner (after activation): participates in N-arylation (Buchwald–Hartwig) and SNAr to give anilines/diarylamines.
  • Protection chemistry: Boc, Cbz, and sulfonamide protections allow orthogonal manipulations.

• Retrosynthetic value

  • Serves as a convergent fragment to introduce a basic nitrogen and a small, rigid hydrophobe (cyclopropyl) in one step, compared with multistep homologations on flexible amines.
  • Enantioenriched requirements: If a single enantiomer is needed, plan for chiral pool synthesis, asymmetric induction at C-2, or resolution of diastereomeric salts/derivatives.

• Selectivity/sterics

  • The α-substitution to nitrogen can influence amide rotamer populations and reaction rates. Slightly reduced basicity vs. unsubstituted piperidine may be observed (qualitative trend), which can benefit selectivity in acylation or alkylation steps.

• Practical notes

  • Convert the HCl salt to the free base for reactions in nonpolar media or with base-sensitive coupling reagents.
  • For late-stage diversification, employ mild conditions to avoid cyclopropane ring opening (acidic or strongly radical conditions can induce opening; plan accordingly).

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biochemical probe with a defined biological target in this listing. No antigen, epitope, species reactivity, clone, or isotype data apply.

Domande frequenti

What is the purity of this product?

This product is supplied at ≥97% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1894128-11-0, the molecular formula is C8H16ClN, and the molecular weight is 161.67 g/mol. InChIKey CPNCCPDSVAKLSZ-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.