cis-(4-Hydroxy-cyclohexyl)-methyl-carbamic Acid tert-Butyl Ester Guide

cis-(4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester is a Boc-protected secondary amine bearing a cis-configured cyclohexanol scaffold, widely employed as a versatile chiral-compatible building block in medicinal chemistry and multi-step organic synthesis.

Chemical Name

cis-(4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester

SKU

C176798

Protecting Group

tert-Butyloxycarbonyl (Boc); removable under mild acidic conditions (e.g., TFA/DCM or HCl/dioxane)

Stereochemistry

cis configuration: hydroxyl and N-methyl-Boc substituents on the same face of the cyclohexane ring

Functional Groups

Secondary carbamate (N-Boc), secondary alcohol (cyclohexanol)

Typical Applications

Building block for CNS drugs, kinase inhibitors, and other bioactive small molecules; serves as electrophile precursor or nucleophile after selective activation

Storage Recommendation

Store in a cool, dry, well-ventilated area away from light and moisture; follow supplier SDS guidelines

Chemical Identity and Structural Features

cis-(4-Hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester (SKU: C176798) is a bifunctional organic compound featuring two key pharmacophoric elements on a cyclohexane ring: a secondary alcohol at the 4-position and a Boc-protected N-methyl amino group at the 1-position. The defining stereochemical feature is the cis relationship between these two substituents, meaning both groups occupy the same face of the cyclohexane ring.

This geometry contrasts with the trans isomer and imparts distinct conformational preferences: the diaxial cis arrangement influences ring pucker, hydrogen-bonding geometry, and three-dimensional presentation of functional groups to biological targets. As a result, cis and trans isomers can exhibit markedly different biological activities, making stereochemical identity a critical quality attribute to verify before use.

The molecular framework contains two independently addressable functional groups — the free hydroxyl for O-functionalization (e.g., esterification, etherification, sulfonylation, or Mitsunobu reactions) and the Boc-masked amine for selective deprotection followed by N-functionalization — enabling orthogonal synthetic manipulations in complex molecule assembly.

Handling, Safety, and Storage Guidelines

Personal Protective Equipment (PPE): When handling cis-(4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester, wear appropriate PPE including nitrile gloves, safety spectacles, and a laboratory coat. If dust or aerosol generation is anticipated, use a half-face respirator with organic vapour/particulate cartridge and conduct operations in a fume hood.

Storage: Store the compound in a tightly sealed container in a cool (ideally 2–8 °C or per supplier SDS), dry, and well-ventilated location away from direct light and incompatible materials such as strong acids and oxidising agents. Boc-protected compounds can be susceptible to hydrolysis under prolonged exposure to acidic or moist conditions; therefore, desiccant packaging is recommended for long-term storage.

Waste Disposal: Dispose of residues and contaminated materials in accordance with local environmental regulations and institutional guidelines. Do not dispose of chemical waste via municipal wastewater systems. Refer to the current Safety Data Sheet (SDS) provided by Aladdin Scientific for full hazard classification, first-aid measures, and regulatory information before commencing work.

Stability Considerations: The Boc carbamate is stable under neutral and basic aqueous conditions and at ambient temperature. Avoid contact with strong protic acids (e.g., trifluoroacetic acid, HCl), which will cleave the Boc group. Thermal stability should be confirmed from the SDS; avoid prolonged heating above recommended temperatures.

Synthetic Applications and Reaction Protocols

Role as a Building Block: This compound functions as a versatile pharmaceutical intermediate owing to its dual reactivity. The free hydroxyl group can be selectively transformed without disturbing the Boc carbamate under appropriate conditions, making it suitable for the introduction of diverse leaving groups or coupling partners. Conversely, Boc removal under standard acidic conditions liberates the free secondary amine for further elaboration.

Common Transformations of the Hydroxyl Group:

• Mesylation/Tosylation: Treatment with methanesulfonyl chloride or tosyl chloride in the presence of triethylamine (CH₂Cl₂, 0 °C to rt) converts the alcohol to a leaving group for subsequent S_N2 displacement or elimination reactions.
• Mitsunobu Reaction: Using DIAD/PPh₃, the hydroxyl can be inverted with retention of the Boc group, enabling access to the trans isomer or O-functionalized derivatives.
• Oxidation: Swern or Dess–Martin periodinane oxidation affords the corresponding ketone for further carbon–carbon bond-forming reactions.

Boc Deprotection Protocol: Dissolve the compound in anhydrous dichloromethane (DCM) and add 20–30% (v/v) trifluoroacetic acid (TFA) at 0 °C; stir at room temperature for 1–2 hours, then concentrate under reduced pressure and neutralise with saturated aqueous NaHCO₃ or use a scavenger resin. Alternatively, treat with 4 M HCl in 1,4-dioxane (1–4 equiv.) for salt precipitation. Confirm complete deprotection by TLC or LC-MS before proceeding.

Note: All reaction conditions described are general literature protocols for Boc-protected amino alcohols; optimise conditions for your specific substrate and scale. Verify compatibility with co-existing functional groups prior to execution.

Quality Control and Analytical Characterisation

Purity Assessment: Confirm compound purity by high-performance liquid chromatography (HPLC) using a reverse-phase C18 column with UV detection (210–220 nm for carbamate absorption). Purity ≥95% is typically required for use in biological assays; for medicinal chemistry hit-to-lead work, ≥98% HPLC purity is preferred.

Identity Confirmation:

• ¹H NMR: Key signals include the broad Boc singlet near δ 1.44 ppm (9H, s, C(CH₃)₃), N-methyl signals (broad, due to restricted rotation), axial/equatorial cyclohexyl protons, and the methine proton adjacent to the hydroxyl (δ ~3.5–3.9 ppm). The cis relationship of substituents is reflected in characteristic coupling constants.
• LC-MS: Confirm the molecular ion [M+H]⁺ or [M+Na]⁺ by electrospray ionisation mass spectrometry. The molecular formula should be consistent with C₁₂H₂₃NO₃ (MW = 229.32 g/mol); confirm against certificate of analysis (CoA).
• Optical Rotation / Chiral HPLC: If enantiopure material is required, verify stereochemical identity by chiral stationary-phase HPLC or optical rotation measurement.

Certificate of Analysis (CoA): Always request and review the CoA from Aladdin Scientific for each lot, verifying purity, melting point (if applicable), NMR consistency, and water content (Karl Fischer titration) before use in critical experiments.

Regulatory Considerations and Procurement

Regulatory Status: cis-(4-Hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester is a research-grade reagent and is not classified as a controlled substance under standard international narcotics or precursor chemical conventions (verify for your jurisdiction). It is intended for research and development use only and is not approved for human therapeutic or veterinary use.

Export/Import Compliance: Purchasers and users are responsible for ensuring compliance with all applicable export control regulations (e.g., EAR, ITAR where relevant) and local import regulations before ordering. Aladdin Scientific recommends consulting your institution's compliance officer for international shipments.

Procurement via Aladdin Scientific: Order SKU C176798 through the Aladdin Scientific online platform or authorised distributors. Provide your institutional billing address, purchase order number, and any required end-user documentation. Bulk quantities and custom packaging may be available — contact the sales team for quotation. Lot-specific CoA and SDS are available upon request at time of order.

Shipping and Handling: The compound is typically shipped at ambient temperature unless otherwise specified on the product page; confirm cold-chain requirements with Aladdin Scientific for large or long-distance orders. Upon receipt, inspect packaging integrity, verify lot number against CoA, and record receipt conditions in your laboratory inventory system.

Frequently asked questions

What is the difference between the cis and trans isomers of (4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester?

In the cis isomer, the hydroxyl group and the N-methyl-Boc substituent are on the same face of the cyclohexane ring, whereas in the trans isomer they are on opposite faces. This stereochemical difference alters the conformational equilibrium, three-dimensional shape, and pharmacological properties of each compound, meaning cis and trans forms can behave very differently in biological assays and chemical reactions. Always confirm the stereochemical identity of your material via NMR coupling constants or chiral HPLC before use.

How do I remove the Boc protecting group from cis-(4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester without damaging the hydroxyl group?

Standard Boc deprotection conditions — such as 20–30% TFA in DCM at 0 °C to room temperature for 1–2 hours, or 4 M HCl in 1,4-dioxane — selectively cleave the Boc carbamate and leave a free secondary alcohol intact, because the tertiary alcohol and secondary alcohol functionalities are stable under these acidic conditions. After deprotection, neutralise the TFA salt with saturated NaHCO3 or use an amine scavenger resin, then extract and dry the product. Monitor conversion by TLC or LC-MS and avoid prolonged reaction times that could lead to side reactions.

How should I store SKU C176798 to maintain its integrity over time?

Store cis-(4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester in a tightly sealed, moisture-resistant container in a cool, dry, and dark location — ideally at 2–8 °C or as specified on the product label and SDS from Aladdin Scientific. Boc groups are susceptible to hydrolysis in the presence of moisture and acid, so inclusion of a molecular sieve or silica gel desiccant is advisable for long-term storage. Always allow the container to equilibrate to room temperature before opening to avoid condensation on the solid.

Can the hydroxyl group of this compound be selectively functionalized without deprotecting the Boc group?

Yes, the free hydroxyl group can be selectively functionalized in the presence of the intact Boc carbamate using reagents that do not generate strongly acidic conditions. For example, mesylation with MsCl/Et3N in DCM, tosylation with TsCl/DMAP, esterification, or Mitsunobu reactions can all be performed selectively on the alcohol while retaining the Boc protecting group, provided reaction temperatures and reagent stoichiometry are carefully controlled. Confirm selectivity for each transformation by monitoring with TLC and LC-MS.

References

1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: New York, 2007. (General reference for Boc protection/deprotection strategies.)
2. Mitsunobu, O. The Use of Diethyl Azodicarboxylate and Triphenylphosphine in Synthesis and Transformation of Natural Products. Synthesis 1981, 1, 1–28.
3. Aladdin Scientific. Certificate of Analysis and Safety Data Sheet for cis-(4-hydroxy-cyclohexyl)-methyl-carbamic acid tert-butyl ester, SKU C176798. (Available from Aladdin Scientific upon request.)

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