(+)-Fluoxetine (22-15-9) Physical and Chemical Properties
(+)-Fluoxetine
The (R)-enantiomer of fluoxetine, supplied as a chiral small-molecule for use in API development, analytical quality control, and chiral synthesis optimization.
| CAS Number | 22-15-9 |
| Family | Aryloxypropanamines (arylpropylamines) |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP |
(+)-Fluoxetine is an optically resolved aryl‑ether tertiary amine belonging to the phenoxypropanamine structural class. The molecule contains a central stereogenic carbon bearing a phenyl substituent and a 4‑(trifluoromethyl)phenoxy group, linked to an N‑methylpropylamino side chain. The presence of a tertiary aliphatic amine imparts basicity and the trifluoromethylated aryl ether motif increases lipophilicity and metabolic stability relative to non‑fluorinated analogues. The compound is the resolved enantiomer corresponding to the (+) sign designation and is the R enantiomer in the IUPAC stereochemical convention.
Electronically, the molecule combines an electron‑rich phenyl ring and an electron‑withdrawing \(-CF_3\) substituent on the pendant aryl ring; this creates modest intramolecular polarity concentrated around the ether oxygen and tertiary amine. The low calculated topological polar surface area, limited hydrogen bond donor count (one secondary/tertiary ammonium hydrogen when protonated), and a computed XLogP3 value indicate a predominantly lipophilic character with sufficient polar functionality to permit protonation and aqueous solubility of the conjugate acid. The tertiary amine is the principal site of protonation and reversible salt formation; under acidic conditions the compound exists primarily as a protonated cation, whereas under neutral to basic conditions the neutral free base predominates.
Functionally, this substance is known for its role as a selective serotonin reuptake inhibitor (SSRI) active ingredient in pharmaceutical applications; it also serves as an intermediate in stereospecific syntheses where the resolved enantiomer is required. Common commercial grades reported for this substance include: EP.
Basic Physicochemical Properties
Density and Solid-State Form
No experimentally established value for this property is available in the current data context.
Qualitatively, as a low‑molecular‑weight organic base with aromatic and aliphatic segments, the substance typically crystallizes as a free base or as crystalline salts (e.g., hydrochloride or other pharmaceutically acceptable acids) depending on processing and isolation conditions. Salt formation of the tertiary amine is commonly used to modify handling, hygroscopicity and dissolution properties.
Melting Point
No experimentally established value for this property is available in the current data context.
Solid‑state melting behavior for tertiary aryl ethers such as this often depends strongly on salt form and enantiomeric purity; racemates and resolved enantiomers can show different melting points and crystalline habits.
Solubility and Dissolution Behavior
No experimentally established value for this property is available in the current data context.
Qualitatively, the neutral free base is expected to have limited intrinsic aqueous solubility due to substantial lipophilicity (see LogP). Protonation of the tertiary amine markedly increases aqueous solubility through formation of water‑soluble salts. Solubility and dissolution rate in formulation contexts are therefore controlled by pH, counterion selection (salt form), and excipient choices (solubilizers, surfactants, solid dispersions).
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context.
The molecule contains a tertiary aliphatic amine as the single basic center; this center undergoes reversible protonation under acidic conditions to give the corresponding ammonium cation. As a tertiary amine, it readily forms stable salts with mineral and organic acids used in pharmaceutical salt formation. Protonation state strongly affects aqueous solubility, partitioning, and interaction with biological targets.
Reactivity and Stability
The aryl‑ether linkage and tertiary amine are the primary functional groups relevant to chemical stability and reactivity. Under typical storage and processing conditions the aryl ether is chemically stable toward routine handling, but can be susceptible to oxidative and metabolic transformations under biological or forced‑degradation conditions. Metabolic N‑demethylation and dealkylation pathways are known for this class; documentation lists N‑demethylated metabolites (e.g., norfluoxetine) and phenolic fragments arising from oxidative cleavage. The presence of a \(-CF_3\) substituent increases resistance to electrophilic aromatic metabolism on the substituted ring. Formulation and processing should minimize exposure to strong acids, strong oxidants, and extremes of temperature and moisture to reduce degradation.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: C17H18F3NO
- Molecular weight: 309.33 \(\mathrm{g}\,\mathrm{mol}^{-1}\)
- Exact/monoisotopic mass: 309.13404868
These values correspond to the neutral free base composition. Salt formation will change the apparent formula and molecular weight per salt stoichiometry.
LogP and Structural Features
- Computed XLogP3: 4
A computed XLogP3 of 4 indicates pronounced lipophilicity consistent with low topological polar surface area (TPSA) and a limited hydrogen bond donor count. Reported computed descriptors: - Topological polar surface area (TPSA): 21.3 - Hydrogen bond donor count: 1 - Hydrogen bond acceptor count: 5 - Rotatable bond count: 6
The combined descriptors imply favorable passive membrane permeability and partitioning into lipophilic phases; protonation significantly increases aqueous solubility and alters effective partitioning.
Structural Identifiers (SMILES, InChI)
- SMILES: CNCCC@HOC2=CC=C(C=C2)C(F)(F)F
- InChI: InChI=1S/C17H18F3NO/c1-21-12-11-16(13-5-3-2-4-6-13)22-15-9-7-14(8-10-15)17(18,19)20/h2-10,16,21H,11-12H2,1H3/t16-/m1/s1
- InChIKey: RTHCYVBBDHJXIQ-MRXNPFEDSA-N
These structural identifiers correspond to the resolved R/(+)-enantiomeric form given by the stereochemical annotation in the SMILES and InChI.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS (as provided in header): 22-15-9
- Additional CAS identifiers appearing in associated records: 100568-03-4
- Deprecated CAS identifiers listed in associated records: 842102-54-9, 847222-29-1, 849322-83-4
- UNII: F279341RUQ
- ChEBI: CHEBI:86991
- ChEMBL: CHEMBL153036
- DrugBank: DB08472
- InChIKey: RTHCYVBBDHJXIQ-MRXNPFEDSA-N
When citing CAS or other registry numbers in procurement or regulatory documentation, confirm the exact stereochemical specification and salt form required (free base vs. specific salt).
Synonyms and Brand-Independent Names
Reported synonyms and related names include: - (R)-Fluoxetine - (+)-fluoxetine - Fluoxetine, (R)- - (R)-Prozac - (3R)-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine - (R)-N-methyl-3-(4-trifluoromethylphenyloxy)-3-(phenyl)propylamine - (R)-(+)-fluoxetine - methyl((3R)-3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)amine
These synonyms reflect the stereochemical, structural and depositor‑supplied naming variants encountered in technical contexts. Use unambiguous identifiers (InChIKey, full IUPAC or CAS with stereochemistry) when specifying procurement of the resolved enantiomer.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
This resolved enantiomer is an active pharmaceutical enantiomer of a selective serotonin reuptake inhibitor (SSRI) class molecule and is used in pharmaceutical research and development where enantiomeric composition is critical. It functions as a serotonin uptake inhibitor and has been studied as the optically active component corresponding to one half of the racemic drug substance.
Formulation and Development Contexts
No concise application summary is available in the current data context; in practice this substance is selected based on its general properties described above.
In formulation development, the free base versus salt state is chosen to balance manufacturability, stability and dissolution. Typical development considerations include selection of a pharmaceutically acceptable salt to increase aqueous solubility and control hygroscopicity, choice of excipients to modulate release, and stereochemical purity assessment for regulatory submission.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Reported commercial grade in associated records: - EP
In addition to pharmacopeial grades (where applicable), standard industry grade concepts apply: pharmaceutical (for clinical or medicinal use), analytical (high purity for characterization), and technical (for intermediates or non‑clinical uses). Selection of grade depends on intended use, regulatory requirements, and impurity profile needs.
General Quality Attributes (Qualitative Description)
Qualitative attributes important for specifications include: - Enantiomeric purity (chiral assay) - Assay of the active free base or specified salt - Residual solvents and volatile organic content controlled per applicable guidelines - Impurity profile including N‑demethylation products and oxidative degradants - Moisture/hygroscopicity, especially for salt forms
Concrete assay limits, impurity thresholds and acceptance criteria should be defined in product‑specific specifications and validated analytical methods.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
No quantitative toxicological thresholds (LD50, occupational exposure limits) are available in the current data context.
Qualitatively, this substance is a pharmacologically active SSRI and should be handled as a bioactive pharmaceutical intermediate or active substance. Potential effects to those exposed may include pharmacodynamic activity at serotonergic targets; therefore, avoid unnecessary exposure. Standard precautions to minimize dermal and inhalation exposure are appropriate: use of gloves, eye protection, and work in a fume hood or local exhaust for powder handling. Avoid environmental release; degradation products and metabolites include norfluoxetine and phenolic fragments.
For detailed hazard, toxicology and regulatory classification, users should consult the product‑specific Safety Data Sheet (SDS) and applicable local legislation.
Storage and Handling Guidelines
Store in a cool, dry, well‑ventilated area, in tightly closed containers protected from light and moisture. Control temperature and humidity to prevent degradation and limit salt‑form conversion or recrystallization. Use appropriate engineering controls when handling the substance in powdered form to prevent dust generation. Dispose of waste in accordance with local regulations.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
