Overview and Chemical Properties

(R)-4-Methoxy-2-methyl-4-oxobutanoic acid (CAS registry; molecular formula C₆H₁₀O₄; MW 146.14 g/mol) is the (R)-enantiomer of the half-methyl ester of 2-methylsuccinic acid. The molecule contains two distinct acid-derived functional groups: a free carboxylic acid at C-1 and a methyl ester at C-4, with a stereocentre at C-2 bearing the (R)-configuration. This bifunctional character makes it an attractive chiral synthon for selective transformations at either end of the carbon backbone.

The compound is a colourless to pale-yellow liquid or low-melting solid at ambient temperature. It is miscible with common polar organic solvents including methanol, ethanol, ethyl acetate, dichloromethane, and acetone, and is sparingly soluble in aliphatic hydrocarbons. The free carboxylic acid moiety confers moderate aqueous solubility, particularly at neutral to basic pH.

Safe Handling and Storage

Personal Protective Equipment (PPE): Wear nitrile or neoprene gloves, safety spectacles with side shields, and a laboratory coat when handling this compound. Work in a well-ventilated fume hood, particularly when preparing concentrated solutions or heating the neat material. Avoid inhalation of vapours and direct contact with skin or eyes.

Storage Conditions: Store the reagent in a tightly sealed container under an inert atmosphere (nitrogen or argon) at 2–8 °C, protected from light and moisture. Prolonged exposure to moisture can promote hydrolysis of the methyl ester functionality. Check the container integrity before each use and record the date of first opening.

Disposal: Dispose of waste material in accordance with local institutional regulations for organic acid waste. Do not pour down the drain without neutralisation and verification of local discharge limits.

Note: Specific GHS hazard classifications and first-aid measures should be verified against the current Aladdin Scientific Safety Data Sheet (SDS) for M709817 prior to use.

Solution Preparation and Handling Protocol

Step 1 – Equilibration: Allow the sealed container to equilibrate to room temperature before opening to minimise condensation of atmospheric moisture onto the reagent.

Step 2 – Weighing: Tare a clean, dry glass vial or weighing boat. Transfer the required quantity of (R)-4-Methoxy-2-methyl-4-oxobutanoic acid using a clean spatula. Record the exact mass. Work quickly to limit atmospheric exposure.

Step 3 – Dissolution: Add the appropriate volume of dry, degassed solvent (e.g., anhydrous dichloromethane or ethyl acetate for synthetic applications; DMSO or acetonitrile for biological assays) to achieve the desired concentration. Mix gently by inversion or vortex at low speed. Sonication at room temperature for 1–2 minutes may be applied if dissolution is slow.

Step 4 – Verification: Confirm complete dissolution by visual inspection. For critical applications, verify concentration by ¹H NMR or titrimetric analysis, and confirm enantiomeric purity by chiral HPLC or optical rotation measurement.

Step 5 – Storage of Solutions: Freshly prepared solutions are recommended. If storage is necessary, seal under inert gas, protect from light, and store at –20 °C. Monitor for signs of ester hydrolysis (formation of the corresponding diacid) during extended storage.

Applications in Research

(R)-4-Methoxy-2-methyl-4-oxobutanoic acid is primarily employed as a chiral building block and synthetic intermediate in the following research contexts:

• Asymmetric synthesis: The (R)-stereocentre and the differentiated carboxylic acid/ester groups allow selective mono-derivatisation, enabling the construction of more complex chiral molecules with defined absolute configuration.
• Pharmaceutical intermediate preparation: Half-esters of alkyl-substituted succinic acids are recurring intermediates in the synthesis of active pharmaceutical ingredients (APIs) requiring defined chirality.
• Peptide and peptidomimetic chemistry: The compound can serve as a non-proteinogenic amino acid surrogate or linker fragment when appropriately functionalised.
• Ligand and catalyst design: Chiral bifunctional acid/ester scaffolds are used in the construction of chiral ligands for asymmetric catalysis.

Researchers are advised to consult primary literature for specific reaction conditions, as optimal parameters will vary by application.

Quality Control and Analytical Characterisation

For applications demanding high enantiomeric purity, the following analytical checks are recommended before use:

Chiral HPLC: Use a suitable chiral stationary phase (e.g., polysaccharide-based columns such as Chiralpak IA, IB, or IC) with a UV-active mobile phase modifier if required. Confirm the enantiomeric excess (ee) against a reference standard or a racemic mixture of (R/S)-4-Methoxy-2-methyl-4-oxobutanoic acid.

Optical Rotation: Measure specific optical rotation [α]_D in an appropriate solvent (e.g., chloroform or methanol) at the sodium D line (589 nm) and compare with literature values for the (R)-enantiomer. Note: specific rotation values should be verified from primary literature; values are not provided in the current source material.

NMR Spectroscopy: Confirm structure by ¹H and ¹³C NMR. Key signals include the methyl doublet at C-2, the methylene protons at C-3, the methoxy singlet of the ester, and the broad carboxylic acid OH signal.

Purity: Assess chemical purity by GC or reverse-phase HPLC. Contact Aladdin Scientific for the certificate of analysis (CoA) corresponding to the specific lot number of M709817.