4-(2,4-Difluorophenoxy)piperidine (CAS: 367501-08-4) is a fluorinated piperidine derivative with the molecular formula C₁₁H₁₃F₂NO and a molecular weight of 213.22 g/mol. Its core structure consists of a piperidine ring linked through an oxygen atom to a 2,4-difluorophenyl group, featuring a secondary amine that remains available for further functionalization. As a key synthetic intermediate, this compound provides the essential 2,4-difluorophenoxy pharmacophore — a critical structural element for achieving high affinity and potency at the G protein-coupled receptor 6 (GPR6) target. The presence of fluorine atoms at the 2 and 4 positions of the phenyl ring imparts enhanced lipophilicity, metabolic stability, and blood-brain barrier penetration, making this scaffold uniquely suited for central nervous system (CNS) drug discovery.
4-(2,4-Difluorophenoxy)piperidine serves as the indispensable building block for the synthesis of GPR6 inverse agonists, most notably CVN424 (solengepras) — a potent, orally active, and brain-penetrant clinical-stage candidate for the treatment of Parkinson‘s disease. The 2,4-difluoro substitution pattern is absolutely critical for potency (EC₅₀ = 38 nM) and brain penetration; simple substitution with other halogenated phenoxy-piperidines leads to a total loss of activity. Market demand is closely tied to the global expansion of Parkinson’s disease therapeutics, the growing interest in GPR6-targeted drug discovery, and the increasing need for specialized CNS-penetrant building blocks in pharmaceutical R&D. Based on its chemical characteristics and industrial chain position, this article systematically analyzes international market dynamics of 4-(2,4-difluorophenoxy)piperidine, focusing on core application scenarios, competitive landscape, regional differences, regulatory trends, and future outlook, providing strategic references for industry participants.
Core Application Fields and Demand
Market demand for 4-(2,4-difluorophenoxy)piperidine is concentrated in two major sectors: pharmaceutical R&D and API intermediate manufacturing (≈85-90% of global consumption) and contract research and custom synthesis (CRO/CDMO) (≈10-15%).
In the pharmaceutical R&D and API intermediate manufacturing sector, this compound serves as the essential building block for GPR6 inverse agonists — an innovative class of therapeutics targeting Parkinson‘s disease. GPR6 is an orphan GPCR predominantly expressed in striatopallidal neurons of the indirect pathway, which is significantly affected by the loss of nigrostriatal dopaminergic neurons in Parkinson’s disease. CVN424 (solengepras), a highly selective, orally active, and brain-penetrant small-molecule GPR6 inverse agonist, directly incorporates this 2,4-difluorophenoxy pharmacophore. Preclinical studies demonstrated that CVN424 produced dose-dependent increases in locomotor activity and restored mobility in bilateral 6-hydroxydopamine models of Parkinson‘s disease. In a phase 2 clinical trial, the 150 mg dose of CVN424 provided a clinically meaningful reduction in daily OFF-time in Parkinson’s disease patients experiencing motor fluctuations, without inducing clinically meaningful adverse effects or dyskinesia. A phase 3 ARISE trial has recently begun dosing, evaluating CVN424 as an adjunctive treatment to levodopa. Additionally, the 4-(2,4-difluorophenoxy)piperidine scaffold has been studied for its ability to act as a catalyst in organic synthesis, its potential as an inhibitor of certain enzymes, and its ability to modulate protein activity. The compound is also used in the synthesis of other biologically active compounds, including selective BTK inhibitors such as PF-06250112. The global Parkinson‘s disease therapeutics market is projected to reach USD 8‑10 billion by 2030, driving sustained demand for key intermediates such as 4-(2,4-difluorophenoxy)piperidine.
In the CRO/CDMO and custom synthesis sector, 4-(2,4-difluorophenoxy)piperidine is used as a customized intermediate for the synthesis of fluorinated heterocyclic libraries, hit-to-lead optimization, and preclinical studies. The compound is also employed in the development of other CNS-targeting pharmaceutical agents, including antipsychotics and antidepressants. The expanding contract research and manufacturing sector in Asia-Pacific, particularly in China and India, further drives volume demand for this specialized building block.
Major Market Participants
The global supply system for 4-(2,4-difluorophenoxy)piperidine follows a pattern of specialized fluorinated heterocyclic intermediate manufacturers, with production concentrated in China, India, Europe, and North America. The compound is generally supplied as a white to off-white solid with purity ranging from 95% to ≥99% (verified by HPLC). Major international suppliers include Sigma-Aldrich, Apollo Scientific, AK Scientific, ChemShuttle, and BenchChem.
Shanghai XinChem Co., Ltd. (XinChem) has established a reliable, fully quality-controlled supply chain for high-purity 4-(2,4-difluorophenoxy)piperidine (CAS 367501-08-4). Our product meets rigorous pharmaceutical intermediate specifications — purity ≥97-99% (HPLC), white to off-white solid, molecular weight 213.22 g/mol, MDL MFCD08687571, with strict control of heavy metals and residual solvents — fully compliant with global CNS drug discovery and pharmaceutical intermediate standards. XinChem is well-positioned to serve the growing global demand from Parkinson‘s disease drug developers, CROs/CDMOs, and academic research institutions.
Regional Market Dynamics
Global demand for 4-(2,4-difluorophenoxy)piperidine shows regional differentiation: “Asia-Pacific dominates production, North America and Europe lead in high-purity R&D and pharmaceutical applications, and Latin America & Middle East/Africa follow as emerging growth markets.”
Asia-Pacific, led by China and India, is the world‘s largest producer of fluorinated heterocyclic intermediates and a rapidly growing consumer. Chinese manufacturers, including XinChem, offer competitive pricing at scales ranging from research quantities to industrial batches, serving both domestic demand for pharmaceutical intermediates and exports to Southeast Asia, Europe, and North America.
North America (United States and Canada) and Europe (Germany, Switzerland, United Kingdom) together account for the largest share of high-purity R&D consumption (≥99%), driven by the highest concentration of GPR6-targeted drug discovery programs and CNS drug development, including the clinical development of CVN424. Customer requirements in these regions are stringent: purity ≥99%, full traceability, ICH Q3D compliance for heavy metals, full impurity profiling, and cGMP documentation for pharmaceutical use.
Regulatory and Environmental Considerations
4-(2,4-Difluorophenoxy)piperidine (CAS 367501-08-4) is classified as an irritant (Xi). The compound may cause irritation to the eyes, skin, and respiratory tract. Recommended storage conditions: 2‑8°C in a tightly sealed, dry, light-protected container under inert atmosphere. Personal protective equipment (PPE) — including chemical-resistant gloves, safety glasses, and respiratory protection — is recommended during handling. The compound should be kept away from fire sources and oxidizing agents.
In the European Union, the compound is subject to REACH regulations; importers and manufacturers must provide Safety Data Sheets (SDS). In the United States, it is regulated under TSCA as a research chemical; for pharmaceutical API use, adherence to cGMP guidelines (21 CFR Parts 210/211) is required. In China, the compound is listed in the Inventory of Existing Chemical Substances (IECSC) and requires safety production licenses for manufacturing facilities. Environmentally, fluorinated organic compounds require responsible handling and disposal; manufacturing generates solvent-containing waste streams requiring proper treatment.
Future Outlook
The market outlook for 4-(2,4-difluorophenoxy)piperidine is tied to three core drivers: (1) the sustained growth of the Parkinson‘s disease therapeutics market, driven by an aging global population and the urgent need for non-dopaminergic therapies; (2) the clinical advancement of CVN424 (solengepras) — with phase 3 trials now underway, successful registration would dramatically increase demand for this key intermediate; and (3) the expanding use of GPR6-targeted drug discovery for other CNS disorders. The compound‘s unique 2,4-difluorophenoxy pharmacophore and its proven role in generating clinical-stage candidates position it for sustained growth in the coming years. Companies that invest in high-purity (≥99%) production capabilities, maintain rigorous impurity documentation for global regulatory filings, and build long-term supply partnerships with Parkinson‘s disease drug developers, CROs, and research institutions will be best positioned to capture value in this expanding market.
Shanghai XinChem Co., Ltd. (XinChem)
As a world-leading supplier of fluorinated organic intermediates, pharmaceutical building blocks, and heterocyclic compounds, Shanghai XinChem Co., Ltd. (XinChem) has always focused on the innovative needs of the CNS drug discovery, pharmaceutical, and CRO/CDMO industries. Relying on core advantages in organic synthesis, fluorination chemistry, quality control, and global logistics, we provide high-quality 4-(2,4-Difluorophenoxy)piperidine (CAS 367501-08-4) to global customers. Our product is manufactured under strict quality management regimes, achieving consistent specifications for pharmaceutical and research grades. Fully compliant with international quality standards, it is the ideal fluorinated building block for GPR6 inverse agonists, including CVN424, and other CNS-targeted therapeutics.
1. Technical Advantages
High Purity & Consistency: Our 4-(2,4-difluorophenoxy)piperidine achieves purity levels of ≥97-99% (verified by HPLC), supplied as a white to off-white solid, molecular weight 213.22 g/mol, MDL MFCD08687571.
Low Impurity Profile: Strict control of residual solvents (<0.5% total), heavy metals (≤10 ppm, ICH Q3D compliant), and related substances by HPLC-UV.
Pharmaceutical-Grade Quality: The compound is tested for full ICH Q3C (residual solvents) and ICH Q3D (heavy metals), with full traceability to primary analytical standards. DMF support is available for pharmaceutical customers.
Batch-to-Batch Uniformity: Rigorous analytical testing (HPLC, NMR, LC-MS, heavy metals by ICP-MS, residual solvents by GC-headspace) guarantees consistent quality and reproducible yields across all production lots.
2. Product Advantages
Essential GPR6 Modulator Building Block: Directly used in the synthesis of GPR6 inverse agonists, including the clinical-stage Parkinson‘s disease candidate CVN424 (solengepras).
Critical 2,4-Difluorophenoxy Pharmacophore: The 2,4-difluoro substitution pattern is essential for potency (EC₅₀ = 38 nM) and brain penetration; generic analogs cannot replicate activity.
Flexible Packaging Options: 250 mg, 500 mg, 1 g, 5 g (glass vials/HDPE containers for R&D); 10 g, 25 g, 50 g, 100 g, 500 g, 1 kg (industrial). Full custom packaging available.
Reliable Supply Chain: Annual capacity in the multi-ton range, with dedicated temperature-controlled warehousing (2‑8°C, dry, light-protected, sealed containers) and just-in-time delivery capabilities.
3. Application Fields
- Pharmaceutical Intermediates: Synthesis of GPR6 inverse agonists (CVN424/solengepras) for Parkinson‘s disease therapy; synthesis of BTK inhibitors (PF-06250112); development of other CNS-targeting APIs, including antipsychotics and antidepressants.
- Parkinson’s Disease Research: GPR6-targeted drug discovery, non-dopaminergic therapeutic strategies, preclinical and clinical development of CVN424.
- GPCR-Targeted Drug Discovery: Building block for GPR6 and other GPCR modulator libraries, SAR studies, and high-throughput screening.
- CRO/CDMO Custom Synthesis: Essential customized intermediate for medicinal chemistry outsourcing, hit-to-lead optimization, and preclinical studies.
4. Service Support
Our technical team provides full impurity profiling (HPLC purity, residual solvents by GC-headspace, heavy metals by ICP-MS, LC-MS identity confirmation), custom purification to any desired specification, and complete regulatory documentation (Certificate of Analysis, Technical Data Sheet, Safety Data Sheet, REACH compliance, TSCA certification, DMF support for pharmaceutical customers). We also offer custom synthesis of fluorinated piperidine derivatives, cold-chain logistics, and just-in-time delivery.
5. Why Choose XinChem
- Professionalism: 20+ years in the pharmaceutical, fluorochemical, and heterocyclic industries.
- Flexibility: Tailored to customer purity specifications, packaging sizes, and regulatory documentation requirements.
- Cost-effectiveness: High quality at competitive industrial pricing.
Contact us now to start cooperation!
Website: www.xinchem.com
Email: sales1@xinchem.com
WhatsApp: +86 18049800532
Post time: Jul-05-2026