3-Cyclopropylmorpholine - ≥95% , CAS No.1260667-05-7

CAS: 1260667-05-7 Cat. No.: C1366358 Formula: C₇H₁₃NO Molecular Weight: 127.18 EC Number: 854-667-5

GRADE & PURITY ≥95%

Storage

Room temperature

Shipped In

Normal

Specifications

Specifications & Purity

≥95%

Storage

Room temperature

Shipped In

Normal

Purity

≥95%

Names and Identifiers

Canonical Smiles

C1CC1C2COCCN2

IUPAC Name

3-cyclopropylmorpholine

InChIKey

KLFPQNHKRHERBF-UHFFFAOYSA-N

INCHI

1S/C7H13NO/c1-2-6(1)7-5-9-4-3-8-7/h6-8H,1-5H2

Molecular Weight

127.18

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Oxazinanes
      • Subclass Morpholines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Oxazinanes
• Subclass: Morpholines
• Intermediate Tree Nodes: Not available
• Direct Parent: Morpholines
• Alternative Parents: Oxacyclic compounds Dialkylamines Dialkyl ethers Azacyclic compounds Organopnictogen compounds Hydrocarbon derivatives
• Molecular Framework: Aliphatic heteromonocyclic compounds
• Substituents: Morpholine - Oxacycle - Azacycle - Secondary amine - Ether - Secondary aliphatic amine - Dialkyl ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Amine - Aliphatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as morpholines. These are organic compounds containing a morpholine moiety, which consists of a six-member aliphatic saturated ring with the formula C4H9NO, where the oxygen and nitrogen atoms lie at positions 1 and 4, respectively.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemical and Physical Properties

• Molecular Weight: 127.180 g/mol
• XLogP3: 0.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 127.1 Da
• Monoisotopic Mass: 127.1 Da
• Topological Polar Surface Area: 21.300 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 101.000
• 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: 1

Application Protocols

Not applicable. No antibody/assay-specific or kit-style protocols are associated with this small-molecule reagent.

• Item-specific tested applications/dilutions: Not specified for this item; refer to CoA/Spec Sheet.
• General lab use notes:
  • For reaction use, see Reaction Conditions and Synthetic Utility tabs for representative procedures.
  • For handling in screening assays, prepare stock solutions in DMSO or MeOH (typical 10–100 mM), filter if needed, and verify concentration by weight or quantitative NMR as appropriate.

Biological Roles

Item-specific biological/biochemical roles are not provided. The points below reflect general knowledge about the motifs present and are not medical claims.

• Morpholine as a motif (general/literature):
  • Commonly used in medicinal chemistry as a polar, basic handle to modulate solubility, target binding through H-bonding, and pKa. The conjugate acid pKa of morpholine is ~8.3; 3-substitution typically leaves basicity in a comparable range.
  • Acts as a bioisostere for dialkylamino groups with reduced lipophilicity; improves aqueous compatibility of otherwise hydrophobic scaffolds.
• Cyclopropyl group (general/literature):
  • Small, conformationally constrained, and metabolically robust; often used to block benzylic or allylic oxidation pathways and to subtly tune steric/electronic properties at a binding site.
• Intrinsic biological activity:
  • As a simple small molecule building block, 3-cyclopropylmorpholine has no defined endogenous biological role. Any biological effects would arise from its incorporation into larger chemotypes.
• Biochemical handling/workup considerations:
  • Protonated salts typically enhance aqueous solubility for biochemical screening; the free base may adsorb to plastics less than highly lipophilic amines but can interact with assay components via basicity.

For any use in biological experiments, ensure appropriate controls, verify purity and counterion content from the item’s CoA, and adhere to the “Research use only” restriction.

Buffer Applications

This compound is not a standard buffering agent. However, as a secondary amine, its conjugate acid exhibits buffering capacity near its pKa.

• Item-specific buffer data: Not specified for this item; refer to CoA/Spec Sheet.
• General/literature notes:
  • Morpholine conjugate acid pKa ≈ 8.3; a 3-substituent typically maintains a pKa in the ~7.8–8.5 range. Thus, solutions of its protonated salt could, in principle, provide limited buffering near pH 8.
  • Unlike dedicated Good’s buffers (e.g., MOPS, HEPES), 3-cyclopropylmorpholine lacks defined buffer capacity specifications, low metal-binding, or low temperature/pKa drift characteristics.
• Practical guidance:
  • For biochemical or electrophoresis applications requiring precise buffering, select established buffers (Tris, MOPS, HEPES). If using this amine in solution, control pH with standard buffers and treat the amine as a reagent, not the buffer component.

Conclusion: Buffer applications are not typically applicable. Use established buffering systems and consider this compound as a reactive/basic additive rather than a buffer.

Green Alternatives

While 3-cyclopropylmorpholine itself is a reagent, greener chemistry can be implemented in reactions where it serves as the amine partner.

Greener choices (literature guidance):

• Solvents:
  • Replace chlorinated solvents (DCM, CHCl3) with EtOAc or MeTHF for acylations and extractions when compatible.
  • Substitute THF with 2-MeTHF or CPME for base-promoted couplings; these offer improved lifecycle metrics and reduced peroxide propensity vs ethers like diethyl ether.
  • Explore water or water–ethanol mixtures for SNAr or reductive amination using phase-transfer or micellar catalysis where feasible.
• Coupling agents and bases:
  • Prefer carbodiimide-free acid activation (e.g., CDI or green peptide coupling reagents) and inorganic bases (K2CO3, Cs2CO3) over strong alkoxides where possible.
• Energy and process:
  • Continuous flow for exothermic acylations and reductive aminations can reduce solvent and improve safety.

Example comparison (general):

• Conventional: Buchwald–Hartwig in dioxane/NaOtBu at 100–110 C.
• Greener variant: Aqueous micellar Pd-catalysis (ppm Pd) or CPME/K3PO4 at lower temperature; simplified workup reduces organic solvent use.

Trade-offs:

• Greener solvents may affect solubility of bases/catalysts, requiring ligand/base optimization.
• Water-rich media may necessitate in situ salt formation; manage amine protonation to maintain reactivity.

Validate alternative conditions on small scale before scale-up.

Pharmaceutical Uses

• Item-specific pharmacopeial status and excipient role: Not specified for this item; refer to CoA/Spec Sheet.
• General context (non-clinical, formulation/manufacturing focus):
  • 3-Cyclopropylmorpholine is primarily a medicinal chemistry building block for discovery and process development. It can be introduced into lead molecules to adjust basicity, polarity, and metabolic profile.
  • Salt selection: Free base can be converted to pharmaceutically relevant salts (e.g., HCl, sulfate, mesylate) during intermediate handling to improve crystallinity, stability, and isolation. Salt choice influences hygroscopicity, melting point, and processability.
  • Impurity considerations: Monitor for N-oxide, over-alkylated tertiary amines, and ring-opened byproducts in synthetic routes; establish purge strategies during scale-up.
  • Workup/isolations: Acid–base extraction facilitates removal of neutral/lipophilic impurities; recrystallization of selected salts can improve purity.
• Manufacturing hygiene (general):
  • Control residual solvents and water (KF) when the compound is carried into later intermediates; define specifications aligned with ICH guidelines during process development.

No therapeutic claims are made. This product is for research and laboratory use only.

Physical Properties

Item-specific specifications are not provided in the Product Data. The following are literature/computational expectations for the neutral free base; verify with the product CoA/SDS before use.

• Phase/appearance: Not specified for this item; refer to CoA/Spec Sheet. (Morpholine derivatives of this size are often low-melting solids or liquids; literature note only.)
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet. (Literature: C7H13NO.)
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Literature: ~127.18 g/mol.)
• Boiling point: Not specified for this item; refer to CoA/Spec Sheet. (Literature expectation for analogous C7 morpholines: moderate BP; actual value should be taken from CoA.)
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• LogP/logD: Not specified for this item; refer to CoA/Spec Sheet. (Literature expectation: cyclopropyl increases lipophilicity relative to morpholine.)
• pKa (conjugate acid): Not specified for this item; refer to CoA/Spec Sheet. (Literature: morpholine conjugate acid pKa ≈ 8.3; 3-substitution typically shifts slightly.)
• Solubility (qualitative, literature):
  • Miscible with many polar organic solvents (MeOH, EtOH, MeCN). Likely soluble in water as the protonated salt; free base shows moderate aqueous solubility due to the basic N.

Note: Use measured values from the product’s CoA/Spec Sheet for any method-critical calculations.

Quality & Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Interpreting common grades (general guidance):
  • Research/technical grade: Suitable for most synthetic and screening workflows; impurity profiles are adequate for discovery chemistry but may not be optimized for trace analytics.
  • Purified or >98% assay (when specified): Appropriate for medicinal chemistry SAR where batch-to-batch reproducibility is critical.
  • HPLC/spectrophotometric grades: Emphasize low UV-absorbing impurities; useful if compound is used as an internal standard or reference for LC/UV workflows.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet. Morpholine derivatives are typically supplied neat without stabilizers.
• Documentation delivered on request:
  • CoA: assay method (e.g., HPLC/GC), residual solvents, water content (KF), and identity (NMR/IR/MS).
  • Spec Sheet: physical constant ranges, appearance, and acceptance criteria.
• Practical QC considerations for this class of compound (general):
  • Identity: 1H/13C NMR should show cyclopropyl signatures (high-field multiplets ~0–1.5 ppm) and morpholine CH2 signals (2.5–4.0 ppm), plus NH signal if not exchanged.
  • Purity: Check for N-oxide (m/z +16) and N-alkylation byproducts via LC–MS. Water content can influence salt formation and handling; verify by KF if critical.

For any regulated or analytical application, rely on the item’s specific CoA/specification sheet.

Reaction & Applications

3-Cyclopropylmorpholine is a versatile secondary amine building block combining a solubilizing morpholine motif with a metabolically stabilizing cyclopropyl group. It is frequently employed in discovery chemistry to tune basicity, polarity, and metabolic soft spots.

Representative application families (literature):

• N-Acylation and N-sulfonylation:
  • Rapid formation of amides/sulfonamides using acid chlorides/anhydrides or sulfonyl chlorides with base (e.g., DIPEA, pyridine). CDI or EDCI/HOBt alternatives for carboxylic acids.
• C–N bond formation to (hetero)aryl electrophiles:
  • Buchwald–Hartwig amination with aryl bromides/chlorides using Pd catalysts (e.g., Pd2(dba)3 or Pd(OAc)2) and dialkylbiaryl phosphines; bases like NaOtBu or Cs2CO3 in toluene/dioxane.
  • SNAr with activated aryl fluorides/nitroarenes in polar aprotics (DMF/DMSO) or water/solvent mixtures.
• Reductive amination (as the amine partner):
  • Coupling with aldehydes/ketones (NaBH3CN or NaBH(OAc)3) to access N-alkyl derivatives.
• Urea/carbamate formation:
  • With CDI, triphosgene, or chloroformates to build ureas/carbamates incorporating the morpholine nitrogen.
• Quaternization/salt formation:
  • Tertiary amines via N-alkylation under controlled conditions; salts (HCl, mesylate, tosylate) for purification and property modulation.

Practical tips:

• Protonation state control is key: free base for nucleophilic coupling; salt forms for handling and purification.
• Cyclopropyl motifs can undergo ring-opening under strongly acidic or radical conditions—avoid harsh conditions during late-stage modifications.
• Monitor for N-oxide formation during aerobic storage; reduce with P(OEt)3 or PPh3 if needed (literature approach).

Reaction Conditions

The following are representative literature conditions when using 3-cyclopropylmorpholine (secondary amine) as a coupling partner. Optimize for your substrate scope.

• Buchwald–Hartwig amination (aryl bromides/chlorides):
  • Catalyst: Pd2(dba)3 (1–2 mol% Pd) or Pd(OAc)2 (2–5 mol% Pd) with dialkylbiaryl phosphine ligands (e.g., XPhos, tBuBrettPhos, or RuPhos, 2–5 mol%).
  • Base: NaOtBu, KOtBu, or Cs2CO3 (2–3 equiv).
  • Solvent: Toluene, dioxane, CPME, or tAmOH; 80–110 C; 4–16 h.
  • Notes: Secondary amines often couple faster than hindered tert-amines; avoid over-alkylation by controlling equivalents.
• SNAr to activated aryl fluorides:
  • Base: K2CO3 or Cs2CO3 (1.5–2.0 equiv).
  • Solvent: DMF/DMSO or MeCN; 50–100 C; 2–20 h.
  • Notes: Water co-solvent can accelerate for highly activated rings; quench with acid then basify for extraction.
• Reductive amination (to give tertiary amines):
  • Conditions: Aldehyde/ketone (1.0 equiv), 3-cyclopropylmorpholine (1.2–1.5 equiv), NaBH3CN (1.5 equiv) in MeOH/AcOH (pH 5–6) or NaBH(OAc)3 in DCE/AcOH; rt–40 C; 2–16 h.
  • Notes: Maintain mildly acidic pH to prevent iminium hydrolysis without fully protonating the amine.
• Acylation/sulfonylation:
  • Reagents: Acid chloride or sulfonyl chloride (1.0–1.2 equiv), base (DIPEA/TEA, 2–3 equiv) in DCM/MeCN/EtOAc; 0 C to rt; 1–4 h.

Expected yields vary with substrate electronics and sterics; many literature examples of morpholine couplings report 60–90% isolated yields after optimization.

Safety & Handling

• GHS classification, pictograms, signal word, and H-statements: Not specified for this item; consult the product SDS for authoritative hazard information.
• General hazards (literature/general):
  • Basic secondary amine; may cause skin/eye irritation and respiratory irritation. Amines can be harmful if swallowed or inhaled. Avoid aerosol formation.
  • Flammability for small amines varies; keep away from ignition sources until SDS confirms classification.
• PPE and engineering controls:
  • Wear safety glasses, lab coat, and suitable gloves (e.g., nitrile). Use in a chemical fume hood to avoid vapor/inhalation exposure.
• Handling guidance:
  • Avoid contact with strong oxidizers and acylating agents unless intended for reaction.
  • Amines can absorb CO2 and moisture; minimize headspace exposure and keep containers tightly closed.
• Incompatibilities (general):
  • Strong acids/bases (can form salts or undergo decomposition under harsh conditions), acid chlorides/anhydrides (acylation), isocyanates (urea formation), and oxidants (N-oxide formation).
• First-aid (overview; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin: Wash with soap and water; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contacts if present and easy to do.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill/leak response:
  • Absorb with inert material (vermiculite, silica). Ventilate area. Dispose per local regulations.

Always consult the current SDS for definitive hazard, exposure limits, and emergency procedures.

Solvent Selection

This product is a nitrogen-containing heterocyclic building block, not a solvent. Solvent choice should be driven by the reaction or purification involving 3-cyclopropylmorpholine.

• Polarity/behavior (general): As a basic secondary amine with an embedded ether, it dissolves readily in polar organics (MeOH, EtOH, MeCN, acetone, DMF, DMSO) and often in moderately polar ethers (THF, 2-MeTHF). Aqueous solubility increases markedly upon protonation (e.g., as the HCl salt).
• Typical solvent choices by application (literature guidance):
  • N-acylation/sulfonylation: DCM, EtOAc, THF, MeCN, or toluene; add base (TEA, DIPEA) when using acid chlorides/anhydrides.
  • Buchwald–Hartwig amination or SNAr: Toluene, dioxane, CPME, or DMAc/DMF depending on catalyst/ligand; water or green co-solvents increasingly used in modern protocols.
  • Salt formation and extractions: Partition between aqueous acid (to protonate) and organic phase (to deprotonate) for efficient workup.
• Comparison notes:
  • Protic vs aprotic: Protic solvents facilitate salt formation and can suppress over-alkylation; aprotic polar solvents enhance nucleophilicity for coupling reactions.
  • Green substitutions: Consider 2-MeTHF/CPME instead of THF/MTBE; EtOAc/MeAc instead of DCM where feasible.

Choose solvents based on catalyst compatibility, desired ionization state, and downstream isolation strategy.

Storage & Reconstitution

• Item-specific storage/shipping (from Product Data):
  • Storage Conditions: Room temperature.
  • Shipped In: Normal.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution:
  • Not applicable; typically supplied neat. If preparing solutions for reactions or screening, dissolve in a suitable dry solvent (e.g., DCM, MeCN, THF, MeOH, DMSO) to the required concentration. Filter through PTFE if particulates are observed.
• General stability guidance (literature/general):
  • Secondary amines are generally stable under ambient conditions but can absorb CO2/H2O from air; keep container tightly closed under inert headspace if long-term storage is anticipated.
  • Protect from strong oxidants. Trace N-oxide formation is possible upon prolonged exposure to air; minimize by storing tightly sealed in a cool, dry place.
  • For extended storage, consider preparing and storing as a crystalline salt (e.g., HCl) to improve shelf stability and handling; convert back to free base as needed.
• Freeze–thaw:
  • Not typically required. If storing solutions (e.g., in DMSO), aliquot to avoid repeated freeze–thaw cycles and store at recommended temperatures for the chosen solvent.

Always consult the product’s CoA/SDS for definitive handling and storage recommendations.

Structure & Identity

3-Cyclopropylmorpholine is a saturated six-membered heterocycle (morpholine: one O and one secondary amine N in a 1,4-relationship) bearing a cyclopropyl substituent at the 3-position of the ring carbon framework.

• Item-specific identifiers (from Product Data):
  • SKU: C1366358
  • Product Name: 3-Cyclopropylmorpholine
  • CAS: 1260667-05-7
  • InChIKey: 183005 (as provided)
  • Storage Conditions: Room temperature; Shipped: Normal
  • Research Use: For research use only
• Structure features (general/literature description):
  • Core ring: morpholine (tetrahydro-1,4-oxazin-4-ium base form; neutral secondary amine as supplied)
  • Substituent: cyclopropyl at C-3 (beta to both heteroatoms), introducing a small, conformationally restricted, lipophilic group.
  • Functional groups: one tertiary ether (ring oxygen), one secondary amine (ring nitrogen).
  • Protonation state: typically neutral free base; readily forms salts with mineral or organic acids (literature).
• Formula and mass (literature/computed for free base):
  • Molecular formula (literature): C7H13NO
  • Molecular weight (literature, monoisotopic ≈/average): ~127.18 g/mol
• Line notations:
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • InChI: Not specified for this item; refer to CoA/Spec Sheet.
• 2D depiction in words: a six-membered ring with alternating –CH2– units interrupted by one O and one NH; at the carbon two atoms away from oxygen (position 3), a cyclopropyl group is attached.

Synthetic Utility

Key reactivity arises from the secondary amine and the adjacent ether within the morpholine ring, combined with a sterically compact cyclopropyl substituent.

• Functional group handles:
  • Secondary amine (nucleophilic): amenable to acylation, sulfonylation, carbamate/urea formation, alkylation, and transition-metal-catalyzed C–N couplings.
  • Ring ether (non-nucleophilic under neutral conditions): confers polarity and H-bond acceptor capability; may direct selectivity in metal-catalyzed couplings via coordination (literature observations for morpholine).
• Typical transformations (literature):
  • Buchwald–Hartwig coupling to aryl halides/pseudohalides.
  • SNAr with activated aryl electrophiles.
  • Reductive amination with carbonyl partners to furnish tertiary morpholines.
  • Formation of morpholinium salts for phase-switch crystallizations or to modulate solubility.
  • Urea/carbamate synthesis using CDI, triphosgene, or chloroformates.
• Strategic value in design:
  • Cyclopropyl group subtly increases steric bulk without large lipophilicity penalty and can “lock” conformations near the morpholine ring; useful for mapping SAR and blocking oxidative liabilities.
• Retrosynthetic considerations:
  • If preparing analogs, late-stage N-functionalization is straightforward; C-3 substitution on morpholine (as present here) is often installed via ring construction (e.g., epoxide opening with cyclopropyl-containing nucleophiles) or via C–H functionalization on protected morpholines (literature), but using this reagent bypasses those steps.

Overall, this building block integrates polarity and compact hydrophobicity for efficient diversification.

Target Specificity

Not applicable. This product is a small-molecule building block and is not supplied as a biological targeting reagent (no antigen/epitope, clone, isotype, or species reactivity).

• Item-specific bio-target data: Not specified for this item; refer to CoA/Spec Sheet if any application testing data are provided.