Name: (4S,5R)-3-(tert-butoxycarbonyl)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid
CAS number 196404-55-4
EINECS number 1592732-453-0
Chemical formula C₂₂H₂₅NO₆
Molecular weight 399.44
InChI=1S/C22H25NO6/c1-22(2,3)29-21(26)23-17(14-8-6-5-7-9-14)18(20(24)25)28-19(23)15-10-12-16(27-4)13-11-15/h5-13,17-19H,1-4H3,(H,24,25)/t17-,18+,19?/m0/s1 Density 1.238 g/cm³ (Predicted value: 1.2±0.1 g/cm³) Boiling point 573.8±50.0 °C at 760 mmHg Flash point 300.8±30.1 °C Water solubility Slightly soluble in water; soluble in organic solvents such as methanol, ethanol, and DMSO Vapor pressure 0.0±1.7 mmHg at 25°C (or 5.25E-14 mmHg at 25°C)
Refractive Index 1.567 (or 1.568)
Storage Conditions 2-8°C, sealed and dry, protected from light
Sensitivity Sensitive to humidity and air, requires inert gas protection
Appearance White to off-white crystalline powder
Specific Gravity 1.238
Color White
BRN No publicly available data
MDL Number MFCD09837613 (or MFCD24387546)
Hazard Symbols No special hazard symbols (general chemicals)
Risk Terms R36/37/38 (Irritation to eyes, respiratory system and skin)
Safety Terms S24/25 (Avoid contact with skin and eyes); S26 (If contact with eyes occurs, immediately flush with plenty of water); S36 (Wear appropriate protective clothing)
Customs Number 2934999090 (Other Heterocyclic Compounds)
II. Properties
(4S,5R)-2-(4-methoxyphenyl)-4-phenyl-3,5-oxazolidinedicarboxylic acid 3-tert-butyl ester is an important chiral oxazolidine derivative with two chiral centers (4S,5R configuration) and a specific rotation of +34° (c=1 in CHCl₃). This compound has a melting point of 134-138°C and is relatively stable at room temperature and pressure, but requires low-temperature storage to prevent degradation.
This compound contains a Boc (tert-butyloxycarbonyl) protecting group, which can be selectively removed under acidic conditions (such as TFA). Its molecule contains a free carboxylic acid group, which can participate in esterification, amidation, and other reactions. The compound is well soluble in organic solvents, especially in DMSO (up to 60 mg/mL), and also has good solubility in methanol and ethanol, but is almost insoluble in water. Its predicted LogP value is 4.20, indicating some lipophilicity.
This compound is sensitive to humidity and air; nitrogen purging is recommended for storage. Under strong acid or alkaline conditions, the oxazolidine ring may open; therefore, extreme pH conditions should be avoided during handling.
III. Uses
This compound is a key chiral side-chain intermediate in the synthesis of docetaxel (trade name Taxotere). Docetaxel is a taxane-based antitumor drug developed by Sanofi and approved by the FDA in 1996. It is widely used to treat various malignant tumors, including breast cancer, lung cancer, prostate cancer, and gastric cancer.
Specific applications include:
Docetaxel semi-synthesis:** As a C-13 side chain, it is linked to the 10-deacetylated bacardine III (10-DAB) core via esterification to construct the complete docetaxel molecular structure.
Cabazitaxel synthesis:** It can also be used to synthesize second-generation taxane drugs such as cabazitaxel.
Drug development:** Used to synthesize docetaxel derivatives and analogues, and to develop novel antitumor drug candidates.
Quality Control: Used as a standard or impurity reference (e.g., cabazitaxel impurity C) for pharmaceutical quality analysis.
IV. Preparation Method: The main synthetic route for this compound uses chiral (2R,3S)-3-phenylisoserine methyl ester as the starting material, and constructs the oxazolidine ring structure through multiple steps:
Main Synthetic Route:
Starting Material: (2R,3S)-N-tert-Butoxycarbonyl-3-phenylisoserine methyl ester (or (2′R,3′S)-phenylisoserine methyl ester)
Acetal Reaction: An addition reaction occurs with 4-methoxybenzaldehyde dimethyl acetal under the catalysis of pyridinium salt of p-toluenesulfonic acid (PPTS) or p-toluenesulfonic acid to form the oxazolidine ring intermediate.
Water Hydrolysis: The intermediate undergoes ester hydrolysis under lithium hydroxide/methanol-water solution or sodium hydroxide/potassium hydroxide conditions.
Crystallization and Purification: High-purity (≥99%) final product is obtained through two recrystallizations (common solvent system: ethyl acetate/n-hexane).
Key Process Parameters:
Reaction Solvent: Toluene, xylene, or DMF
Catalyst: PPTS or p-toluenesulfonic acid
Alkaline Hydrolysis: LiOH/MeOH/H₂O system, 20°C, 2 hours, yield 90-95%
Overall Yield: Approximately 68% (calculated from starting material)
Quality Control: Purity is determined by HPLC, and the ee value is determined by chiral HPLC to ensure that the chiral purity meets the standards for pharmaceutical intermediates.
GHS Hazard Category: Non-hazardous, general chemicals
Main Hazards: May cause irritation to eyes, skin, and respiratory tract.
Handling Protection: Wear protective gloves, goggles, and a dust mask; handle in a fume hood.
First Aid Measures: Skin contact: Immediately wash with soap and plenty of water; Eye contact: Immediately flush with plenty of water for at least 15 minutes; Inhalation: Move to fresh air; Ingestion: Seek immediate medical attention.
Fire Protection Measures: Use dry powder, carbon dioxide, or foam extinguishers; avoid direct water flow.
Spill Handling: Wear protective equipment, absorb with inert material, collect in a closed container, and treat as chemical waste.
Waste Disposal: Dispose of according to local regulations; recommended to use a qualified hazardous waste disposal facility.
Stability: Stable at room temperature; avoid contact with strong oxidizers, strong acids, and strong bases.
Incompatible Materials: Strong oxidizers, strong acids, and strong bases.
Annual Production Capacity: 5 tons/year (can be expanded to 10 tons/year based on market demand)
Single Batch Output: 50-200 kg
Delivery Time: Spot goods: 3-5 working days; Custom orders: 2-4 weeks
Storage and Transportation Cold chain transportation at 2-8°C, equipped with temperature recorders, ensures stable product quality.
Quality Assurance Commitment:
All products undergo rigorous quality testing to ensure compliance with pharmaceutical intermediate standards.
A 24-month quality guarantee period is provided.
A comprehensive batch traceability system is in place, enabling full traceability from raw materials to finished products.
A professional technical team provides 24/7 technical support and after-sales service.
Post time: May-29-2026
