Handling & Use Protocol for Fluorinated Lactone Dibenzoate R177832

((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate is a stereodefined, fluorinated γ-butyrolactone dibenzoate ester serving as a key chiral intermediate in the synthesis of fluorinated nucleoside analogs and other complex bioactive molecules.

SKU

R177832

Chemical Name

((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate

Compound Class

Fluorinated γ-butyrolactone dibenzoate; chiral synthetic intermediate

Stereocenters

Three defined stereocenters: 2R, 3R, 4R

Key Functional Groups

Lactone (γ-butyrolactone), two benzoate esters, quaternary C–F bond at C-4

Primary Application

Chiral building block for fluorinated nucleoside analog synthesis and medicinal chemistry

Recommended Storage

Cool, dry, dark conditions; tightly sealed under inert atmosphere (see protocol below)

Chemical Identity and Structural Features

((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate (SKU R177832) is a chiral, fluorinated tetrahydrofuran-2(3H)-one (γ-butyrolactone) derivative bearing two benzoate ester protecting groups. The molecule features a five-membered lactone ring with three contiguous stereocenters at positions C-2 (R), C-3 (R), and C-4 (R), along with a quaternary carbon bearing both a fluorine atom and a methyl group at C-4. This quaternary C–F motif confers significant conformational rigidity and metabolic stability, properties that are highly desirable in medicinal chemistry and nucleoside analog design.

The two benzoyl (Bz) groups serve as hydroxyl-protecting groups on the C-3 oxygen and the C-2 hydroxymethyl appendage, allowing selective downstream deprotection. The overall stereochemical arrangement mimics the d-configured ribose or related sugar scaffold found in biologically active nucleoside drugs, making this compound a versatile precursor in antiviral and anticancer research programs.

Safety, Handling, and Storage Protocol

Personal Protective Equipment (PPE)

• Wear appropriate chemical-resistant gloves (nitrile recommended), safety goggles or face shield, and a laboratory coat at all times when handling this compound.
• Work in a well-ventilated fume hood to minimize inhalation exposure to fine particulates or vapors.

Receiving and Inspection

1. Upon receipt, inspect the package for damage or moisture ingress before opening.
2. Record the lot number, quantity, and condition in your laboratory inventory system.
3. If the material appears discolored, clumped, or otherwise compromised, contact Aladdin Scientific customer support before use.

Storage Conditions

• Store in a tightly sealed container under an inert atmosphere (nitrogen or argon) to prevent hydrolysis of the lactone and benzoate ester groups.
• Keep in a cool (2–8 °C recommended as a conservative guideline; confirm with current CoA), dry, and dark location away from moisture, light, and incompatible reagents such as strong acids, bases, and nucleophiles.
• Avoid repeated freeze-thaw cycles; aliquot into single-use portions where feasible.

Waste Disposal

Dispose of all waste containing this compound in accordance with applicable local, national, and institutional regulations for organic chemical waste. Do not pour down the drain.

Typical Laboratory Applications and Reaction Protocol

Role as a Synthetic Intermediate

This compound functions primarily as an advanced chiral intermediate for the synthesis of 4'-fluorinated nucleoside analogs. The benzoate protecting groups can be selectively cleaved under mild basic conditions (e.g., methanolic ammonia or sodium methoxide in methanol at low temperature), revealing the corresponding free hydroxyl groups for glycosylation or further functionalization. The fluorine at the quaternary C-4 position is not directly reactive under standard nucleophilic substitution conditions, contributing to the stability of the core scaffold during multistep synthesis.

General Deprotection Procedure (Benzoate Removal)

1. Dissolution: Dissolve R177832 in anhydrous methanol or another suitable dry solvent (e.g., THF/MeOH mixture) at a concentration appropriate for your scale (typical range 0.05–0.5 M). Use oven-dried glassware and handle under inert gas.
2. Reagent addition: Add a mild base such as sodium methoxide (0.1–0.5 equiv. relative to substrate) or methanolic ammonia solution dropwise at 0 °C with stirring. Monitor the reaction progress by TLC (suitable eluent system: ethyl acetate/hexanes) or HPLC.
3. Quenching: Once deprotection is judged complete (typically 30 min to several hours depending on conditions), quench the reaction by addition of a weak acid such as acetic acid to neutralize excess base.
4. Workup: Evaporate solvent under reduced pressure. Partition the residue between ethyl acetate and water, separate layers, wash the organic phase with saturated aqueous sodium bicarbonate and brine, dry over anhydrous MgSO₄ or Na₂SO₄, filter, and concentrate.
5. Purification: Purify by silica gel column chromatography using an appropriate gradient. Confirm product identity and purity by ¹H NMR, ¹³C NMR, ¹⁹F NMR, and HRMS.

Note: Specific reaction conditions, stoichiometry, and temperatures should be optimized empirically for each application. The above represents a general guideline only.

Quality Control and Analytical Characterization

Recommended Analytical Methods

Before use in sensitive synthetic applications, researchers should verify the identity and purity of R177832 using the following methods:

• ¹H NMR and ¹³C NMR: Confirm the connectivity and relative stereochemistry of the lactone ring, benzoate groups, methyl, and CH₂OBz substituents. Run in CDCl₃ or DMSO-d₆ as appropriate.
• ¹⁹F NMR: Verify the presence and chemical environment of the quaternary C–F at C-4. The unique quaternary fluorine environment should give a characteristic signal distinguishable from common fluorine impurities.
• HPLC Purity: Assess purity by reversed-phase HPLC (C18 column, UV detection at 230 nm or 254 nm to capture benzoate chromophores). Compare against the Aladdin Certificate of Analysis (CoA) specification.
• HRMS or MS: Confirm the molecular ion consistent with the molecular formula. Exact molecular weight should be verified against the CoA provided with each lot.
• Optical Rotation: Measure specific optical rotation in an appropriate solvent (e.g., CHCl₃ or MeOH) and compare with the CoA value to confirm enantiomeric integrity.

Always request and review the Certificate of Analysis (CoA) for each lot before use. Contact Aladdin Scientific if analytical data do not meet your specifications.

Frequently asked questions

What are the recommended storage conditions for R177832?

R177832 should be stored in a tightly sealed container under an inert atmosphere (nitrogen or argon) in a cool, dry, and dark environment to prevent hydrolysis of the lactone and ester functionalities. Refrigeration (2–8 °C) is a conservative guideline; always defer to the specific conditions stated on the current Certificate of Analysis supplied with your lot.

How can the benzoate protecting groups be removed from R177832?

The benzoate esters can be cleaved under mild basic conditions, such as treatment with methanolic ammonia or a catalytic amount of sodium methoxide in anhydrous methanol at low temperature (0 °C to room temperature). Progress should be monitored by TLC or HPLC, and the reaction should be quenched with a weak acid after completion. Exact conditions should be empirically optimized for each specific application and scale.

Why is the quaternary C-4 fluorine important in this compound?

The quaternary C–F bond at C-4 introduces conformational rigidity to the tetrahydrofuran ring and provides metabolic stability to derivatives synthesized from this intermediate, because C–F bonds at quaternary carbons are highly resistant to enzymatic defluorination. These properties are strategically exploited in the design of fluorinated nucleoside analogs with improved pharmacokinetic profiles.

Which analytical techniques are essential for characterizing R177832?

Essential analytical techniques include ¹H NMR, ¹³C NMR, and ¹⁹F NMR for structural confirmation, reversed-phase HPLC for purity assessment, HRMS for molecular formula verification, and optical rotation measurement to confirm stereochemical integrity. All results should be compared against the Certificate of Analysis provided by Aladdin Scientific for the specific lot received.

Is R177832 air- and moisture-sensitive?

Yes. The lactone ring and benzoate ester groups are susceptible to hydrolysis in the presence of moisture and may be sensitive to nucleophilic reagents. It is recommended to handle R177832 under an inert atmosphere using dry solvents and glassware, and to store it sealed under nitrogen or argon. Minimize exposure to atmospheric humidity during weighing and transfer operations.

References

1. Aladdin Scientific. Product Information and Certificate of Analysis for R177832: ((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate. Aladdin Scientific Corp.
2. Fluorinated nucleoside analogs in medicinal chemistry: general textbook-level background on C-F bond properties and benzoate protecting group strategies in carbohydrate and nucleoside chemistry.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.