Manufacturer: Hangzhou Royalchem Co.,LTD.
Website: www.cnroyalchem.com
【 Providing a complete set of intermediates and impurities for Ticagrelor 】
【 Providing a complete set of intermediates and impurities for Ticagrelor 】
【 Providing a complete set of intermediates and impurities for Ticagrelor 】
Here is a detailed product description for (1R,2R)-Ethyl 2-(3,4-difluorophenyl)cyclopropanecarboxylate (CAS 1006376-61-9):
1. Chemical Identification: * CAS Registry Number: 1006376-61-9 * Systematic Name: Ethyl (1R,2R)-2-(3,4-difluorophenyl)cyclopropane-1-carboxylate * Synonyms: * (1R,2R)-Ethyl 2-(3,4-difluorophenyl)cyclopropanecarboxylate * rel-(1R,2R)-Ethyl 2-(3,4-difluorophenyl)cyclopropanecarboxylate (if relative stereochemistry is emphasized) * Ethyl (1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxylate * Molecular Formula: C₁₂H₁₂F₂O₂ * Molecular Weight: 226.22 g/mol
2. Structural Features: * Core Structure: A cyclopropane ring. * Substituent 1: A 3,4-difluorophenyl group attached to one carbon (C2) of the cyclopropane ring. This group provides aromatic character, lipophilicity, and potential for specific interactions via the fluorine atoms. * Substituent 2: An ethyl ester group (-COOCH₂CH₃) attached to the adjacent carbon (C1) of the cyclopropane ring. This ester group is polarizable and can serve as a synthetic handle (hydrolysis to acid, transesterification, amidation). * Stereochemistry: The compound is the (1R,2R) enantiomer. This specifies the absolute spatial configuration of the two chiral centers (C1 and C2 of the cyclopropane ring). The relative positions of the phenyl and carboxylate groups are trans to each other across the cyclopropane ring. Enantiomeric purity is a critical characteristic for biological activity and specific applications.
3. Physical Properties (Typical Expectations - Specifics vary by grade/purity): * Physical State: Colorless to pale yellow liquid or low-melting solid at room temperature. (The exact state often depends on purity and storage). * Boiling Point: Estimated > 200 °C (decomposition likely before boiling). * Melting Point: Not prominently reported; likely low if liquid at RT. * Density: ~1.2 g/cm³ (estimated). * Refractive Index: ~1.50 (estimated). * Solubility: * Soluble in common organic solvents (e.g., Dichloromethane (DCM), Chloroform (CHCl₃), Ethyl Acetate (EtOAc), Acetone, Methanol (MeOH), Ethanol (EtOH), Tetrahydrofuran (THF), Dimethylformamide (DMF), Dimethyl Sulfoxide (DMSO)). * Very low solubility in water. * Optical Rotation: [α]₂₀ᴰ will have a specific non-zero value (e.g., +XX° or -XX°) dependent on concentration and solvent (e.g., CHCl₃ or EtOH). The magnitude and sign are key indicators of enantiomeric purity and identity for the (1R,2R) isomer. [Actual value must be confirmed per specific batch analysis] .
4. Chemical Properties: * Reactivity: The ester group is hydrolyzable (acidic or basic conditions) to the corresponding carboxylic acid. It can undergo transesterification or reduction (e.g., DIBAL-H to aldehyde). The cyclopropane ring, while strained, is relatively stable but can undergo ring-opening reactions under strong acidic conditions, catalytic hydrogenation, or with certain transition metals. The aromatic ring can undergo electrophilic substitution (though fluorines are moderately deactivating/ortho-para directing). * Stability: Generally stable under ambient conditions when stored properly. Sensitive to strong acids, strong bases, strong oxidizing agents, and prolonged exposure to light/heat. Moisture may lead to slow ester hydrolysis. * Chirality: High enantiomeric excess (ee) is typically required for its intended applications. Chiral purity must be specified and verified (e.g., by Chiral HPLC or NMR with chiral shift reagent).
5. Synthesis: * Primarily synthesized via enantioselective methods to control the (1R,2R) configuration. Common approaches include: * Asymmetric Simmons-Smith Cyclopropanation: Reaction of a chiral allylic alcohol derivative (e.g., (E)-3-(3,4-difluorophenyl)prop-2-en-1-ol) with a zinc carbenoid (e.g., EtZn/CH₂I₂) in the presence of a chiral catalyst (e.g., Chiral disulfonamide, bisoxazoline). * Chiral Auxiliary Approach: Using a chiral auxiliary attached to the carboxylate precursor before cyclopropanation, followed by auxiliary removal and esterification. * Purification typically involves chromatography (e.g., silica gel, preparative HPLC) and/or crystallization.
6. Applications: * Key Pharmaceutical Intermediate: This is its predominant use. The (1R,2R) stereoisomer is a crucial building block in the synthesis of more complex molecules, particularly: * Protease Inhibitors: It is a well-established advanced intermediate in the synthesis of potent Hepatitis C Virus (HCV) NS3/4A Protease Inhibitors (e.g., precursors to compounds like Paritaprevir, Grazoprevir, Glecaprevir, Voxilaprevir). The cyclopropane moiety and specific stereochemistry are essential for binding to the enzyme active site. * Potential precursor to other bioactive molecules targeting similar enzymes or receptors where a rigid, lipophilic trans-disubstituted cyclopropane with fluorinated aryl is beneficial. * Medicinal Chemistry Research: Used extensively in drug discovery programs exploring cyclopropane-containing scaffolds with fluorinated aromatic groups. * Chiral Chemistry Studies: Serves as an example or starting material in studies of asymmetric synthesis, cyclopropanation reactions, or chiral separation techniques.
7. Handling and Storage: * Handling: Use in a well-ventilated fume hood. Wear appropriate personal protective equipment (PPE): safety glasses, gloves (nitrile), and lab coat. Avoid contact with skin, eyes, and clothing. Avoid inhalation of vapor or mist. Avoid ingestion. * Storage: Store tightly sealed in a cool (< 8°C, refrigerator or freezer recommended for long-term stability), dry, well-ventilated place. Protect from moisture and light. Keep away from heat, sparks, open flames, and strong oxidizing agents. Store under an inert atmosphere (e.g., Nitrogen, Argon) for prolonged storage stability, especially to minimize ester hydrolysis. * Shelf Life: Stable for months to years when stored as recommended. Monitor purity periodically.
8. Safety Considerations: * Hazards: Combustible liquid. May be harmful if swallowed, in contact with skin, or if inhaled. May cause skin and eye irritation. Potential occupational hazard if dust/vapor is generated. Specific toxicological data (LD50, etc.) is typically limited, so treat with caution as per standard laboratory practices for organic compounds. * First Aid: Eyes: Rinse cautiously with water for several minutes. Skin: Wash with soap and plenty of water. Inhalation: Move to fresh air. Ingestion: Rinse mouth; do NOT induce vomiting; seek medical advice. Consult Safety Data Sheet (SDS) for specific first aid measures. * Fire Fighting: Use alcohol-resistant foam, dry powder, or carbon dioxide (CO₂). Water spray may be ineffective but can be used to cool containers. * Accidental Release: Contain spillage. Absorb with inert material (e.g., sand, vermiculite, spill pillows), then place in suitable container for disposal. Prevent entry into drains/sewers/waterways. Ventilate area.
