Buy 4‑methylpiperidin‑4‑ol (CAS 3970-68-1)
Buy 4‑methylpiperidin‑4‑ol (CAS 3970-68-1)
- Pharmaceutical Synthesis: It is an essential core intermediate used to build central nervous system (CNS) active agents, including novel antipsychotics and antidepressants.
- Agrochemicals: It serves as a foundational starting material for the formulation of specialty insecticides and herbicides.
- Chemical Reactivity: The hydroxyl group acts as a potent nucleophile in organic reactions, while the methyl group is used to fine-tune the steric and electronic properties of target molecules. [1, 2]
Researchers appreciate 4-Methylpiperidin-4-ol for its favorable properties, including its stability and reactivity, which facilitate a range of chemical reactions. Its application extends to the development of novel materials and chemical processes, making it an essential compound for both academic research and industrial applications. With its ability to improve product performance and streamline synthesis, 4-Methylpiperidin-4-ol stands out as a valuable asset in the toolkit of chemists and industry professionals alike.
4-METHYLPIPERIDIN-4-OL Basic Attributes
115.176
115.099716
DTXSID30576304
2933399090
Characteristics
32.3
-0.1
0.976±0.06 g/cm3
184.4°C at 760 mmHg
79.5±11.0 °C
1.465
H2O: Freely soluble (693 g/L) (25 ºC)
Safety Information
P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P405, P501
H314
|Danger|H314 (100%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]|P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P405, and P501|Aggregated GHS information provided by 3 companies from 1 notifications to the ECHA C&L Inventory.
4-METHYLPIPERIDIN-4-OL Use and Manufacturing
A mixture of the Cbz protected piperidine mt 3-1 (1.5 g, 6.02 mmol) and Pd/C (0.3 g) in methanol (30 mL) was degassed under reduce pressure and purged with hydrogen 358times. The reaction mixture was stirred under hydrogen (50 psi) at room temperature overnight. The reaction mixture was filtered through a pad of Celite and the filtrate wasconcentrated under reduce pressure to provide compound mt 3-2 (500 mg, 72percent), which was used for next step without further purification. MS-ES (m/z): 116.3(M+H) .4-methyl-piperidin-4-ol (Intermediate 79b)A solution of Intermediate 79a (5.50 g, 25.6 mmol) in TFA (20 mL) and DCM (40 mL) was stirred at RT for 1 h. The reaction mixture was applied to SCX- 2 cartridges (2 70 g) and washed with MeOH. The product was eluted with 2M NHSynthesis of compound 221.3. To a solution of 221.2 (1.3 g, 6.04 mmol, l .Oeq) in CHTo a stirred solution of 2- (5-amino-2- (furan-2-yl) -7H-pyrazolo [4, 3-e] [1, 2, 4] triazolo [1, 5-c] pyrimidin-7-yl) -2-phenylpropanoic acid (100 mg, 0.26 mmol) , HATU (108 mg, 0.28 mmol) and DIEA (100 mg, 0.78 mmol) in THF (15 ml) was added General procedure: Et3N (0.045 mL, 0.320 mmol) and 3-methylbutan-1-amine (0.037 ml, 0.320 mmol) were added to 5-((1, 2, 3, 5, 6, 7-hexahydro-s-indacen-4-yl)amino)-1-((2-(trimethylsilyl)- ethoxy)methyl)-1H-1, 2, 4-triazole-3-sulfonyl chloride (Intermediate B4) (100 mg, 0.213 mmol) in DCM (4 mL) at 0 C. The reaction was stirred for 1 h and concentrated in vacuo. TFA (1 mL) was added and the reaction was stirred at RT for 1 h. The product was purified by basic prep HPLC (5-50% MeCN in water) to afford the title compound (1.8 mg, 2% yield) as a pale white solid.LCMS m/z 390.2 (M+H)+ (ES+); 388.2 (M-H)- (ES-).1H NMR (DMSO-d6) d 8.77 (s, 1H), 7.72 (s, 1H), 6.94 (s, 1H), 2.94 (t, J = 7.4 Hz, 2H), 2.82 (t, J = 7.4 Hz, 4H), 2.64 (t, J = 7.3 Hz, 4H), 1.97 (p, J = 7.4 Hz, 4H), 1.63 – 1.51 (m, 1H), 1.29 (q, J = 7.2 Hz, 2H), 0.82 (d, J = 6.6 Hz, 6H). One exchangeable proton not observedFormation of 1-[4-[(3S)-4-(2-amino-6-methyl-pyrimidin-4-yl)-1, 4-oxazepan-3-yl]-3-chloro-phenyl]-[0S21] To a stirred solution of 4-(2′-(tert-butyl)-[3, 4′-bipyridin]-5-yl)-3-chlorobenzoic acid (100 mg, 0.4098 mmol) in DMF(1 ml) was added HATU (622.8 mg, 1.639 mmol) and DIPEA (158.8 mg, 1.229 mmol). After stirring for 10 min, To a stirred solution of 2-(chloromethyl)-N-(2, 4-dimethoxybenzyl)imidazo[1, 2- c]quinazolin-5-amine (90 mg, 0.235 mmol) in acetonitrile (2351 mul) was added 4- methylpiperidin-4-ol (54.2 mg, 0.470 mmol) and potassium carbonate (97 mg, 0.705 mmol). The reaction mixture was heated to 80 C with stirring for 4 hrs, then cooled to ambient and filtered. The solvent was evaporated and the residue was redissolved in DCM and washed with NaHCO3 (aq) to give crude product which was used in the next step without purification, LC/MS = 462 [M+1].General procedure: To a round-bottomed flask equipped with a magnetic stir bar wereadded 20c or 20f (1.0 eq), 22a-d or 24a-b (1.2 eq), DIPEA (2.0 eq), and DMA (1.0 M). The reaction vessel was immersed in a 100 C preheatedoil bath for 12 h until the reaction was completed as determinedby TLC. After cooling, the reaction was diluted with water and extractedwith ethyl acetate. The ethyl acetate layer was washed withsaturated brine and dried over anhydrous MgSO4. After filtration andconcentration, the crude product was purified on a silica gel column toafford 25a-j.General procedure: To a round-bottomed flask equipped with a magnetic stir bar wereadded 20c or 20f (1.0 eq), 22a-d or 24a-b (1.2 eq), DIPEA (2.0 eq), and DMA (1.0 M). The reaction vessel was immersed in a 100 C preheatedoil bath for 12 h until the reaction was completed as determinedby TLC. After cooling, the reaction was diluted with water and extractedwith ethyl acetate. The ethyl acetate layer was washed withsaturated brine and dried over anhydrous MgSO4. After filtration andconcentration, the crude product was purified on a silica gel column toafford 25a-j. 4.1.14.1. 4-Hydroxy-4-methyl-N-(3-(4-(methylcarbamoyl)phenoxy)-5-(trifluoromethyl)phenyl)piperidine-1-carboxamide (25a). Coupling of20c (243 mg, 0.5 mmol) with 22a (69 mg, 0.6 mmol) in the presenceof DIPEA afforded 25a (160 mg, 62%), eluted with hexane/ethylacetate (1/5, V/V). White solid, M.P. 103-106 C. 1H NMR (400 MHz, CDCl3) delta 7.91 (d, J=8.8 Hz, 2H), 7.50 (s, 1H), 7.40 (s, 1H), 7.27 (s, 1H), 7.12 (d, J=8.7 Hz, 2H), 6.98 (s, 1H), 6.61 (s, 1H), 3.79-3.72 (m, 2H), 3.42-3.32 (m, 2H), 3.06 (s, 3H), 1.67-1.61 (m, 4H), 1.31 (s, 3H).13C NMR (101 MHz, DMSO) delta 165.80, 158.15, 156.81, 154.07, 143.60, 130.51 (d, J=32.3 Hz), 130.16, 129.33, 123.79 (d, J=273.7 Hz), 118.42, 112.05, 110.59, 107.92, 66.02, 40.34, 38.21, 29.70, 26.23.HRMS (ESI) m/z [M+Na]+ calcd. for C22H25F3N3O4 452.1792, found452.1787.
Computed Properties
Molecular Weight:115.17
XLogP3:-0.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:115.099714038
Monoisotopic Mass:115.099714038
Topological Polar Surface Area:32.3
Heavy Atom Count:8
Complexity:76.6
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes
Safety Data Sheets (SDS)
The SDS provides comprehensive safety information on handling, storage, and disposal of the
2,2,6,6-Tetramethyl-4-piperidinol
Tert-butyl 4-nitropiperidine-1-carboxylate
Select this compound for its orthogonal Boc protection—stability under basic/nucleophilic conditions with selective TFA-labile deprotection enables streamlined multi-step synthesis. Direct catalytic hydrogenation (H₂, Pd/C) yields N-Boc-4-aminopiperidine without premature deprotection, critical for kinase inhibitor and PROTAC assembly. Unlike unprotected 4-nitropiperidine or hydrochloride salt, the Boc group prevents undesired side reactions and ensures regiochemical control during spirocyclization. Batch-specific CoA (NMR, HPLC, GC) provided. Long-term storage stability (2–8°C) supports kilogram-scale procurement campaigns.
Technical Parameters
Basic Identity
| Product Name | Tert-butyl 4-nitropiperidine-1-carboxylate |
|---|---|
| CAS | 1228630-89-4 |
| Molecular Formula | C10H18N2O4 |
| Molecular Weight | 230.264 |
Structural Identifiers
| SMILES | CC(C)(C)OC(=O)N1CCC(CC1)[N+](=O)[O-] |
|---|---|
| InChI | InChI=1S/C10H18N2O4/c1-10(2,3)16-9(13)11-6-4-8(5-7-11)12(14)15/h8H,4-7H2,1-3H3 |
| InChIKey | XASYUHHGRZOCKH-UHFFFAOYSA-N |
Commercial & Availability
| Standard Pack Sizes | 100 mg / 250 mg / 1 g / 5 g / Bulk Custom |
|---|---|
| Availability | In Stock |
| Custom Synthesis | Available on request |
Structure & Identifiers
Tert-butyl 4-nitropiperidine-1-carboxylate (CAS 1228630-89-4): Overview and Procurement Context
Tert-butyl 4-nitropiperidine-1-carboxylate (CAS 1228630-89-4), also known as N-Boc-4-nitropiperidine or 1-(tert-butoxycarbonyl)-4-nitropiperidine, is an N-protected 4-nitropiperidine derivative with the molecular formula C10H18N2O4 and a molecular weight of 230.26 g/mol [1]. It belongs to the class of N-Boc-protected heterocyclic building blocks, wherein the tert-butyloxycarbonyl (Boc) group protects the piperidine nitrogen, leaving the 4-nitro group available for selective reduction or further functionalization . This compound is primarily utilized as a synthetic intermediate in medicinal chemistry and pharmaceutical research, with applications spanning the synthesis of kinase inhibitor scaffolds, GPCR-targeting ligands, and spiropiperidine analogues [2].
- [1] PubChem. 2-Methyl-2-propanyl 4-nitro-1-piperidinecarboxylate. Compound Summary. CID: 44118500. View Source
- [2] BOC Sciences. tert-Butyl 4-Nitropiperidine-1-carboxylate – CAS 1228630-89-4. Building Block Product Page. View Source
Why tert-Butyl 4-nitropiperidine-1-carboxylate Cannot Be Simply Substituted with Unprotected or Alternative N-Protected 4-Nitropiperidines
Generic substitution of tert-butyl 4-nitropiperidine-1-carboxylate with alternatives such as unprotected 4-nitropiperidine, 4-nitropiperidine hydrochloride (CAS 1881295-85-7), or other N-protected variants (e.g., Cbz- or Fmoc-protected) introduces quantifiable risks in synthetic workflow efficiency, chemoselectivity, and downstream purity . Unprotected 4-nitropiperidine exhibits a secondary amine (pKa ~10-11) that can undergo undesired side reactions during multi-step sequences, including nucleophilic addition to electrophilic intermediates or premature metal coordination, necessitating additional protection/deprotection steps that reduce overall yield [1]. The Boc group of tert-butyl 4-nitropiperidine-1-carboxylate offers a specific acid-labile orthogonal protection strategy: it remains stable under basic and nucleophilic conditions but can be selectively removed with TFA/DCM (typically 20-50% TFA) without affecting benzyl ethers, silyl ethers, or other base-labile protecting groups commonly employed in complex molecule synthesis [2]. In contrast, the hydrochloride salt form, while commercially available, imposes solubility constraints in aprotic organic solvents and introduces counterion management complexities that impact reaction reproducibility at scale. The quantitative evidence below substantiates these differentiation points for informed procurement decisions.
- [1] Isidro-Llobet A, Alvarez M, Albericio F. Amino acid-protecting groups. Chemical Reviews. 2009;109(6):2455-2504. View Source
- [2] Master Organic Chemistry. Amine Protection and Deprotection – Boc, Cbz, and Fmoc. 2021. View Source
Quantitative Differentiation Evidence: tert-Butyl 4-nitropiperidine-1-carboxylate vs. Closest Analogs
N-Boc Protection Enables 4-Aminopiperidine Synthesis with Prevention of Spontaneous Self-Condensation
The Boc protection of tert-butyl 4-nitropiperidine-1-carboxylate serves as a latent form of 4-aminopiperidine, preventing the spontaneous self-condensation and oligomerization that occurs when unprotected 4-aminopiperidine is stored or handled under ambient conditions [1]. 4-Aminopiperidine in its free base form undergoes rapid intermolecular reactions (e.g., Schiff base formation with trace carbonyl impurities, or oxidation) leading to purity degradation within hours to days; the Boc-protected nitro precursor remains stable under recommended storage conditions (2-8°C), enabling long-term inventory management and reproducible synthetic outcomes [2]. This protection strategy is particularly critical for multi-step pharmaceutical syntheses where 4-aminopiperidine must be generated in situ immediately prior to coupling reactions .
| Evidence Dimension | Handling stability and prevention of self-condensation |
|---|---|
| Target Compound Data | Stable solid; recommended storage at 2-8°C with no decomposition under inert atmosphere; nitro group remains intact until selective reduction is performed [2] |
| Comparator Or Baseline | Unprotected 4-aminopiperidine (free base): undergoes self-condensation and oxidation within hours at room temperature, requiring immediate use or stringent inert storage |
| Quantified Difference | Storage stability extended from hours (free amine) to months (Boc-protected nitro precursor); reduction can be performed on-demand to generate 4-aminopiperidine in situ with reported yields of 80-95% for analogous N-Boc-4-nitropiperidine reductions using Pd/C and H₂ [3] |
| Conditions | Class-level inference based on established Boc-protection chemistry principles and comparative stability of protected vs. unprotected aliphatic amines; validated by vendor storage specifications [2] |
Why This Matters
Procurement of the Boc-protected nitro precursor rather than unprotected 4-aminopiperidine eliminates the risk of batch-to-batch variability from decomposition, ensuring reproducible downstream yields in medicinal chemistry campaigns.
- [1] Wuts PGM, Greene TW. Greene’s Protective Groups in Organic Synthesis. 4th ed. John Wiley & Sons; 2006. Chapter 7: Protection for the Amino Group. View Source
- [2] GLPBIO. tert-butyl 4-nitropiperidine-1-carboxylate. Chemical Properties and Storage Conditions. Storage: 2-8°C. View Source
- [3] Gallou F, et al. High Turnover Pd/C Catalyst for Nitro Group Reductions in Water. One-Pot Sequences and Syntheses of Pharmaceutical Intermediates. Organic Process Research & Development. 2021. View Source
Solubility Profile in Organic Solvents Distinguishes Boc-Protected Derivative from Hydrochloride Salt Form
tert-Butyl 4-nitropiperidine-1-carboxylate demonstrates markedly different solubility characteristics compared to 4-nitropiperidine hydrochloride (CAS 1881295-85-7), a commonly considered alternative . The Boc-protected derivative is freely soluble in a broad range of aprotic organic solvents including dichloromethane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide—solvents routinely employed in palladium-catalyzed couplings, nucleophilic substitutions, and reductions . In contrast, 4-nitropiperidine hydrochloride exhibits limited solubility in aprotic organic media and typically requires aqueous or protic solvent systems (e.g., methanol, water) for dissolution, which are incompatible with many water-sensitive reagents and catalytic transformations . This solubility differential translates directly to reaction medium flexibility and compatibility with standard synthetic protocols in medicinal chemistry workflows.
Batch-to-Batch Quality Consistency Enabled by Vendor-Supplied Analytical Certification
Commercial suppliers of tert-butyl 4-nitropiperidine-1-carboxylate (CAS 1228630-89-4) provide batch-specific analytical documentation including ¹H NMR (400 MHz in CDCl₃), HPLC purity assessment (≥95% to ≥98% depending on grade), and GC analysis, enabling direct verification of identity and purity prior to use in critical synthetic sequences . This level of quality documentation is not uniformly available for less common or custom-synthesized 4-nitropiperidine derivatives, where users must independently validate identity and purity—a time-consuming and resource-intensive process. The availability of standardized analytical data, including a published ¹H NMR spectrum in CDCl₃ for direct comparison, reduces the risk of misidentification and ensures that procurement decisions are based on verified material quality rather than supplier claims alone .
Orthogonal Deprotection Compatibility Enables Sequential Functionalization Without Competing Side Reactions
The Boc group of tert-butyl 4-nitropiperidine-1-carboxylate provides orthogonal protection that is stable under conditions that cleave alternative protecting groups such as Cbz (hydrogenolysis) or Fmoc (base), while being selectively removable under mild acidic conditions (TFA/DCM, 20-50% TFA at room temperature) without affecting acid-sensitive functional groups when appropriately scavenged [1]. This orthogonality is quantifiably advantageous in multi-step sequences: the Boc group remains intact during nitro reduction (H₂, Pd/C) and subsequent N-alkylation or acylation steps, allowing the piperidine nitrogen to be unmasked only at the final stage of synthesis [2]. In contrast, alternative N-protected 4-nitropiperidines (e.g., Cbz-protected) would undergo concurrent deprotection during catalytic hydrogenation of the nitro group, leading to unprotected 4-aminopiperidine that can participate in undesired side reactions [3].
| Evidence Dimension | Chemoselectivity of deprotection relative to nitro reduction |
|---|---|
| Target Compound Data | Boc group stable under H₂/Pd-C nitro reduction conditions; deprotection orthogonal (acid-labile, base-stable, hydrogenolysis-stable) [1] |
| Comparator Or Baseline | Cbz-protected 4-nitropiperidine: Cbz group undergoes hydrogenolytic cleavage under the same H₂/Pd-C conditions used for nitro reduction, resulting in simultaneous deprotection and potential side reactions [3] |
| Quantified Difference | Sequential functionalization possible: Boc-protected → nitro reduction (Boc intact) → N-functionalization → Boc deprotection; Cbz-protected: nitro reduction and deprotection occur concurrently, eliminating a synthetic handle |
| Conditions | Class-level inference based on established protecting group orthogonality principles; H₂ (1 atm), Pd/C (5-10 mol%), room temperature [1][2] |
Why This Matters
The orthogonal stability profile of the Boc group enables stepwise, controlled functionalization of the piperidine scaffold, a critical requirement for the systematic SAR exploration of piperidine-containing drug candidates.
Regioselective Reduction of Nitro Group Over Boc-Deprotection: Pd/C-Catalyzed Hydrogenation Selectivity
Under standard catalytic hydrogenation conditions (H₂, 1 atm, Pd/C), tert-butyl 4-nitropiperidine-1-carboxylate undergoes selective reduction of the 4-nitro group to the corresponding 4-amino derivative without concomitant cleavage of the N-Boc protecting group [1]. This chemoselectivity is quantifiable: reactions employing 0.4-5 mol% Pd/C in solvents such as methanol or water achieve nitro-to-amine conversion with reported yields of 80-95% for structurally analogous N-Boc-4-nitropiperidines, while Boc group integrity remains >95% intact as confirmed by NMR analysis of the crude reaction mixture [2]. This selectivity contrasts with the behavior of N-benzyl-protected 4-nitropiperidines, where hydrogenolytic N-debenzylation competes with or outpaces nitro reduction under identical conditions, necessitating alternative reduction protocols (e.g., SnCl₂, Zn/HCl) that may compromise functional group tolerance [3].
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