N-4-Boc-aminocyclohexanone: Properties, Uses & FAQs

N-4-Boc-aminocyclohexanone is a versatile, Boc-protected aminocyclohexanone building block widely employed as a synthetic intermediate in medicinal chemistry and drug discovery campaigns.

Chemical Name

tert-butyl (4-oxocyclohexyl)carbamate

CAS Number

179321-49-4

Molecular Formula

C₁₁H₁₉NO₃

Molecular Weight

213.27 g/mol

Appearance

White to off-white crystalline solid

Key Functional Groups

Ketone (C=O) and Boc-protected amine (NHBoc)

SKU

N134328

What Is N-4-Boc-aminocyclohexanone?

N-4-Boc-aminocyclohexanone (IUPAC: tert-butyl (4-oxocyclohexyl)carbamate; CAS 179321-49-4) is an alicyclic compound featuring a cyclohexanone ring bearing a tert-butoxycarbonyl (Boc)-protected amino group at the 4-position. The Boc group serves as an acid-labile protecting group for the primary amine, allowing selective deprotection under mild acidic conditions (e.g., trifluoroacetic acid or 4 M HCl in dioxane) without disturbing other base- or hydrogenolysis-sensitive functionalities.

The molecule presents two orthogonal handles for further elaboration: the electrophilic ketone carbonyl, which is amenable to nucleophilic addition, reductive amination, condensation, and Wittig-type reactions; and the latent free amine, revealed upon Boc removal, which can participate in acylation, sulfonylation, and further coupling reactions. This bifunctionality makes N-4-Boc-aminocyclohexanone a highly sought-after scaffold in the construction of complex, sp³-rich pharmaceutical intermediates.

Applications in Synthesis and Drug Discovery

The compound is primarily used as a building block in medicinal chemistry and process chemistry. Key synthetic applications include:

• Reductive amination: The ketone reacts with primary or secondary amines in the presence of a reducing agent (e.g., NaBH₃CN or NaBH(OAc)₃) to install diverse amine substituents on the cyclohexane ring, providing rapid access to 4-aminocyclohexylamine derivatives after Boc deprotection.
• Nucleophilic addition: Grignard and organolithium reagents add to the ketone carbonyl to yield tertiary alcohol intermediates bearing the protected amine, useful in the synthesis of CNS-active compounds and kinase inhibitor scaffolds.
• Condensation reactions: The ketone undergoes Wittig, HWE, and related olefination reactions, enabling access to exocyclic alkene intermediates.
• Fragment-based and scaffold-hopping strategies: The sp³-rich, bicyclizable core is valuable in fragment-based drug discovery (FBDD) programs where increased three-dimensionality is desired to improve selectivity and reduce attrition.

The compound appears frequently as a key intermediate in the synthesis of protease inhibitors, GPCR ligands, and other therapeutic targets that incorporate a 4-substituted cyclohexylamine motif.

Handling, Storage and Safety

Storage: Store N-4-Boc-aminocyclohexanone in a tightly sealed container at 2–8 °C or at room temperature in a cool, dry place, protected from light and moisture. Under recommended conditions the compound is stable for at least 24 months. Long-term storage at –20 °C is advisable for maximum shelf life.

Handling: Use standard laboratory personal protective equipment (PPE): lab coat, nitrile gloves, and safety glasses. Work in a well-ventilated fume hood when weighing or dissolving the material to avoid inhalation of fine dust. The compound is not classified as acutely toxic under standard GHS criteria, but as with all fine chemicals, avoid ingestion, inhalation, and prolonged skin contact.

Solubility: Freely soluble in common organic solvents including dichloromethane, THF, ethyl acetate, methanol, DMSO, and acetonitrile. Sparingly soluble in water. Typical stock solutions are prepared in DMSO (up to ~100 mM) or DCM for synthetic use.

Stability considerations: The Boc group is stable under basic and neutral conditions but cleaves readily in strong acid (e.g., TFA/DCM, HCl/dioxane). Avoid prolonged exposure to acidic conditions unless intentional deprotection is desired. The ketone is stable to ambient moisture under normal laboratory conditions.

Purity, Specification and Quality

Aladdin Scientific supplies N-4-Boc-aminocyclohexanone (SKU: N134328) with purity typically ≥97% as determined by HPLC and/or NMR analysis. Each lot is accompanied by a Certificate of Analysis (CoA) specifying appearance, purity, melting point, and NMR data. Researchers requiring higher purity for sensitive assays should contact our technical team to inquire about custom specifications.

Characterization data for reference: ¹H NMR (400 MHz, CDCl₃) exhibits characteristic signals for the cyclohexanone ring protons, the NH proton (broad), and the Boc tert-butyl singlet near δ 1.45 ppm. The carbonyl stretching frequency appears near 1710–1720 cm⁻¹ (ketone) and ~1690 cm⁻¹ (carbamate C=O) in the IR spectrum.

Lot-specific CoAs are available for download from the Aladdin Scientific website product page using the lot number printed on the label. If additional analytical data (e.g., GC, elemental analysis, chiral HPLC) are required, please submit a request through our customer service portal.

Ordering and Availability

N-4-Boc-aminocyclohexanone is available from Aladdin Scientific under SKU N134328. Multiple pack sizes are typically stocked to meet the needs of both discovery-scale (mg quantities) and process-scale (gram quantities) projects. For bulk or custom quantities, please contact our sales team for a quotation.

Orders can be placed directly through the Aladdin Scientific online store, by purchase order via email, or through approved procurement platforms. Standard shipping is performed at ambient temperature with appropriate desiccant packaging; cold-chain shipping can be arranged upon request. International orders are subject to applicable export regulations and may require additional lead time.

For questions regarding pricing, availability, documentation, or technical specifications, please contact Aladdin Scientific customer service or refer to the product page on our website.

Frequently asked questions

What is the CAS number for N-4-Boc-aminocyclohexanone?

The CAS registry number for N-4-Boc-aminocyclohexanone (tert-butyl (4-oxocyclohexyl)carbamate) is 179321-49-4. This number can be used to confirm identity when cross-referencing with supplier databases or literature sources.

How do I remove the Boc protecting group from N-4-Boc-aminocyclohexanone?

Boc deprotection is routinely achieved by treating the compound with a strong acid such as trifluoroacetic acid (TFA, 20–50% v/v) in dichloromethane for 30–60 minutes at room temperature, or with 4 M HCl in 1,4-dioxane. After deprotection, the resulting amine is typically isolated as its TFA or HCl salt. The free base can be obtained by basification with triethylamine, aqueous sodium bicarbonate, or a polymer-supported scavenger prior to workup.

What solvents are suitable for dissolving N-4-Boc-aminocyclohexanone?

N-4-Boc-aminocyclohexanone dissolves readily in common organic solvents including dichloromethane (DCM), tetrahydrofuran (THF), ethyl acetate, methanol, acetonitrile, and DMSO. It is sparingly soluble in water. For biological assay stock solutions, DMSO is the most common choice, typically at concentrations up to approximately 100 mM; confirm compatibility with your assay system before use.

What reactions can be performed on the ketone group of N-4-Boc-aminocyclohexanone?

The ketone carbonyl of N-4-Boc-aminocyclohexanone is reactive toward a broad range of transformations, including reductive amination with primary and secondary amines, nucleophilic addition of organometallic reagents (Grignard, organolithium), reduction to the alcohol (NaBH₄, L-Selectride), Wittig and Horner–Wadsworth–Emmons olefination, and condensation with hydroxylamine or hydrazines to form oximes or hydrazones. These reactions enable rapid diversification of the cyclohexane core for library synthesis.

How should N-4-Boc-aminocyclohexanone be stored to maintain stability?

Store the compound in a tightly sealed container at 2–8 °C, in a cool and dry location, away from light and moisture. For long-term archiving, storage at –20 °C is recommended. Avoid exposure to strong acids, which will cleave the Boc protecting group. Under these conditions, the compound is expected to remain stable for at least 24 months.

Is N-4-Boc-aminocyclohexanone available as a single enantiomer or as a racemate?

The 4-aminocyclohexanone core bearing a Boc group at the 4-position is a planar-symmetric (achiral) ketone when the ring is in its symmetric chair conformation; however, the amine-bearing carbon can exist in cis/trans isomeric forms in reduced derivatives. The commercially available material supplied by Aladdin Scientific under SKU N134328 should be confirmed by the lot-specific CoA for any stereochemical designation. Please contact our technical team for clarification on stereochemical purity if required for your application.

References

1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: New York, 2007.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012.
3. Abdel-Magid, A. F.; Mehrman, S. J. A Review on the Use of Sodium Triacetoxyborohydride in the Reductive Amination of Ketones and Aldehydes. Org. Process Res. Dev. 2006, 10, 971–1031. doi:10.1021/op0601007

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