(cis)-Ethyl 3-Hydroxycyclobutanecarboxylate: Handling & Use Guide

(cis)-ethyl 3-hydroxycyclobutanecarboxylate is a stereodefined cyclobutane building block bearing both a hydroxyl and an ethyl ester functional group in a cis relationship, making it a versatile chiral-ready intermediate for medicinal chemistry and total synthesis applications.

Product Name

(cis)-ethyl 3-hydroxycyclobutanecarboxylate

SKU

C174594

Molecular Formula

C7H12O3

Molecular Weight

144.17 g/mol

Key Functional Groups

Secondary alcohol (hydroxyl) and ethyl ester in cis configuration

Stereochemical Descriptor

cis (1,3-relationship of OH and CO2Et on cyclobutane ring)

Typical Storage Condition

Cool, dry place; refrigeration (2–8 °C) recommended for long-term stability

Primary Application

Synthetic intermediate for pharmaceutical and agrochemical research

Chemical Identity and Stereochemistry

(cis)-Ethyl 3-hydroxycyclobutanecarboxylate (SKU C174594) is a cyclobutane-based difunctional compound with the molecular formula C₇H₁₂O₃ and a molecular weight of approximately 144.17 g/mol. The molecule features a strained four-membered carbocyclic ring substituted at the 1-position with an ethyl ester (–CO₂Et) and at the 3-position with a secondary hydroxyl group (–OH).

The cis descriptor indicates that both substituents occupy the same face of the cyclobutane ring, conferring a specific three-dimensional geometry that distinguishes this compound from its trans diastereomer. This stereochemical definition is critical in medicinal chemistry contexts where binding-pocket complementarity depends on precise spatial orientation of functional groups. Researchers should verify the stereochemical purity (diastereomeric ratio) by NMR or chiral HPLC before use in stereoselective transformations.

The cyclobutane ring itself imparts conformational rigidity compared with open-chain analogs, a property increasingly exploited in drug design to reduce entropic penalties upon target binding and to improve metabolic stability.

Handling, Storage, and Safety Guidelines

Storage: Store (cis)-ethyl 3-hydroxycyclobutanecarboxylate in a tightly sealed container in a cool (2–8 °C), dry, and well-ventilated location away from heat sources and direct sunlight. Prolonged exposure to moisture or elevated temperatures may promote ester hydrolysis or oxidation of the alcohol moiety. For long-term archival storage, consider an inert atmosphere (nitrogen or argon) to minimize oxidative degradation.

Handling: Standard laboratory precautions apply. Wear appropriate personal protective equipment (PPE) including chemical-resistant gloves, safety glasses, and a lab coat when handling this reagent. Work in a well-ventilated fume hood when weighing or transferring the compound to minimize inhalation exposure. Avoid contact with skin, eyes, and mucous membranes.

Stability: The ethyl ester group is susceptible to base- or acid-catalyzed hydrolysis; avoid prolonged exposure to strongly acidic or basic aqueous conditions unless hydrolysis is the intended transformation. The secondary hydroxyl group may undergo oxidation under harsh oxidizing conditions. Check the certificate of analysis (CoA) supplied with each lot for purity data and recommended use-by date.

Disposal: Dispose of waste material in accordance with local, national, and institutional regulations for organic chemical waste. Do not pour down the drain without verifying local discharge limits.

Synthetic Applications and Reactivity

(cis)-Ethyl 3-hydroxycyclobutanecarboxylate is valued as a bifunctional building block that allows orthogonal manipulation of its two functional groups—the hydroxyl and the ester—enabling diverse synthetic pathways.

Ester transformations: The ethyl ester can be hydrolyzed to the corresponding carboxylic acid under standard saponification conditions (e.g., aqueous NaOH or LiOH), or reduced to the primary alcohol using reagents such as LiAlH₄ or DIBAL-H. Amide coupling from the derived carboxylic acid provides access to cyclobutane-containing amide scaffolds relevant to drug discovery.

Hydroxyl group elaboration: The secondary –OH can be protected as a silyl ether (TBS, TMS), benzyl ether, or acetal. It can also be activated as a mesylate or tosylate for subsequent S_N2 displacement, enabling inversion of configuration where stereochemical control is required. Mitsunobu conditions (DIAD/PPh₃) allow stereochemical inversion with retention of substitution pattern. Oxidation to the ketone (e.g., Swern, Dess–Martin, or TEMPO/NaOCl) furnishes ethyl 3-oxocyclobutanecarboxylate, a useful intermediate for further functionalization.

Ring-opening and strain-release strategies: While the cyclobutane ring is generally stable under mild conditions, strain-release functionalization strategies can be applied under specific conditions in transition-metal-catalyzed reactions, making cyclobutane fragments attractive bioisosteres for gem-dimethyl groups or cyclohexane in drug design.

Pharmaceutical relevance: Cyclobutane carboxylates and hydroxy cyclobutanes appear as structural motifs in several drug candidates and approved pharmaceuticals, driving demand for stereodefined building blocks such as this compound in medicinal chemistry programs.

Quality, Purity, and Analytical Verification

Each lot of (cis)-ethyl 3-hydroxycyclobutanecarboxylate (C174594) supplied by Aladdin Scientific is accompanied by a Certificate of Analysis (CoA) specifying purity (typically assessed by GC or HPLC), appearance, and batch-specific analytical data. Researchers should request and review the CoA prior to use.

Recommended analytical checks before use:

• 1H and 13C NMR: Confirm structure and stereochemical assignment. The cis relationship of the hydroxyl and ester substituents should be verifiable by coupling constant analysis (cyclobutane proton coupling patterns are diagnostic) or by comparison with published spectral data.
• Diastereomeric purity: Assess by 1H NMR integration (if signals are resolved) or chiral stationary-phase HPLC to confirm the cis/trans ratio meets your experimental requirements.
• GC or HPLC purity: Confirm absence of significant impurities, including the trans diastereomer, residual solvents, and starting materials from synthesis.
• Karl Fischer titration: If moisture sensitivity is a concern for your application, determine water content before use.

If the compound does not meet required specifications, contact Aladdin Scientific customer service to arrange re-analysis or replacement under our returns and refunds policy.

Ordering, Specifications, and Customer Support

(cis)-Ethyl 3-hydroxycyclobutanecarboxylate is available from Aladdin Scientific under SKU C174594. To place an order, visit the Aladdin Scientific website, search by SKU or product name, select the required pack size, and proceed through the standard checkout process. Bulk quantities and custom pack sizes may be available upon request—contact our sales team for pricing and lead times.

Pricing and promotions: Current pricing, available pack sizes, and any applicable promotional discounts or reward-point schemes are displayed on the product page at time of purchase. Promotional pricing is subject to change; confirm final pricing at checkout.

Shipping and delivery: This reagent is typically shipped at ambient temperature with appropriate packaging. However, refrigerated shipping (cold pack) is recommended for orders requiring long transit times to preserve product quality. Confirm shipping conditions with Aladdin Scientific at the time of order if your location requires expedited or temperature-controlled delivery.

Returns and refunds: If you receive product that does not match the stated specifications or is damaged in transit, contact Aladdin Scientific customer service within the applicable returns window. Please retain original packaging and the CoA for reference when initiating a return.

Technical support: For questions about this product's suitability for specific reactions, compatibility with your workflow, or interpretation of analytical data, contact Aladdin Scientific's technical support team via the website contact form or by email.

Frequently asked questions

What is the difference between the cis and trans isomers of ethyl 3-hydroxycyclobutanecarboxylate?

In the cis isomer (C174594), the hydroxyl group at the 3-position and the ethyl ester at the 1-position of the cyclobutane ring are on the same face of the ring, whereas in the trans isomer they are on opposite faces. This difference in relative configuration results in distinct physical properties (e.g., melting point, polarity) and different reactivity profiles in stereoselective reactions, making the choice of isomer critical for applications requiring defined stereochemistry in the product.

How should I confirm the stereochemical purity of (cis)-ethyl 3-hydroxycyclobutanecarboxylate before use?

The most reliable methods are chiral stationary-phase HPLC, which can resolve and quantify the cis and trans diastereomers, and 1H NMR spectroscopy, where the coupling constants of the cyclobutane ring protons are diagnostic for the relative configuration. Comparing your acquired spectrum with published reference data or an authentic sample further confirms assignment. The Aladdin Scientific CoA for each lot provides baseline purity data, but additional in-house diastereomeric purity testing is recommended for sensitive stereoselective applications.

Can the ethyl ester group be selectively transformed without affecting the hydroxyl group?

Yes. By first protecting the hydroxyl group as a silyl ether (e.g., TBS-Cl, imidazole) or other compatible protecting group, you can then perform selective ester manipulations such as saponification, reduction, or aminolysis on the ester functionality. Alternatively, under mild reducing conditions (e.g., DIBAL-H at low temperature), the ester can be selectively reduced to an aldehyde. Careful selection of reagents and conditions, combined with an appropriate hydroxyl-protection strategy, allows orthogonal functionalization of both groups.

What solvents are suitable for dissolving (cis)-ethyl 3-hydroxycyclobutanecarboxylate?

This compound is expected to be soluble in common polar organic solvents such as ethanol, methanol, ethyl acetate, dichloromethane, acetone, and THF, owing to its ester and hydroxyl functionality. Solubility in nonpolar solvents such as hexane is expected to be limited. Aqueous solubility is moderate and pH-dependent due to potential ester hydrolysis under acidic or basic aqueous conditions. Always verify solubility experimentally at your target concentration before use.

References

1. Lovering, F.; Bikker, J.; Humblet, C. Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success. J. Med. Chem. 2009, 52, 6752–6756. doi:10.1021/jm901241e
2. Stepan, A. F. et al. Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor. J. Med. Chem. 2012, 55, 3414–3424. [Cited here as general context for strained-ring bioisostere strategy in medicinal chemistry.] doi:10.1021/jm300094r
3. Aladdin Scientific Certificate of Analysis for (cis)-ethyl 3-hydroxycyclobutanecarboxylate, SKU C174594. Aladdin Scientific, Shanghai. [Internal document; available upon request from Aladdin Scientific.]

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