Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate

Product Name Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate
Alias BIX01294
Mininmum Order 1mg
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
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Manufacturer Bouling Chemical Co., Limited
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In terms of specification, Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate is supplied with purity ≥98% (HPLC) and characterization data (NMR, MS), making it suitable for medicinal chemistry and lead optimization studies.

Specifications

HS Code	664924
Chemical Formula	C19H24BrNO4S
Molecular Weight	442.37
Appearance	Typically a solid (description may vary based on purity and conditions)
Melting Point	Specific value requires experimental determination
Solubility In Water	Expected to be low (organic compound with non - polar groups)
Solubility In Organic Solvents	Likely soluble in common organic solvents like dichloromethane, ethyl acetate
Density	Data would need to be experimentally determined
Vapor Pressure	Low vapor pressure due to its relatively large molecular size
Stability	Stable under normal conditions, but may react with strong oxidizing or reducing agents

As an accredited Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100 g of Ethyl 2-(3 - Bromo - 4 - Isobutoxyphenyl)-4 - Methyl - 5 - Thiazolecarboxylate in sealed chemical - grade bag.
Shipping	Ethyl 2-(3 - Bromo - 4 - Isobutoxyphenyl)-4 - Methyl - 5 - Thiazolecarboxylate is shipped in specialized containers. Precautions are taken to ensure safe transit due to its chemical nature, with proper labeling and compliance to shipping regulations.
Storage	Ethyl 2-(3 - Bromo - 4 - Isobutoxyphenyl)-4 - Methyl - 5 - Thiazolecarboxylate should be stored in a cool, dry place away from direct sunlight. Keep it in a tightly sealed container to prevent moisture and air exposure, which could potentially degrade the chemical. Store it separately from incompatible substances to avoid reactions. Ensure the storage area has proper ventilation.

Application of Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate

In the synthesis of febuxostat, a xanthine oxidase inhibitor regulated under USP monograph guidelines and FDA 21 CFR 211 current Good Manufacturing Practice requirements, ethyl 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate serves as the pivotal aryl bromide intermediate installed prior to palladium-catalyzed cyanation. On commercial-scale campaigns executed in glass-lined or Hastelloy C-276 reactors with a minimum pressure rating of 6 bar(g), the substrate is charged at a molar ratio of 1.0 equivalent relative to the limiting reagent in the subsequent coupling vessel, with zinc cyanide (0.55–0.60 equivalents) or potassium hexacyanoferrate(II) trihydrate (0.22–0.25 equivalents, accounting for the equivalent weight contribution of three cyanide donors) as the cyanating agent. The downstream transformation proceeds in anhydrous N,N-dimethylformamide containing ≤ 0.01 wt% water by Karl Fischer titration, utilizing tetrakis(triphenylphosphine)palladium(0) at a catalyst loading of 0.5–2.0 mol% with respect to the bromide. A jacketed reactor equipped with a retreat-curve impeller and a nitrogen sparge ring maintains an internal temperature of 105 ± 3 °C for 6–10 hours; endpoint determination relies on in-process HPLC monitoring with a C18 column (150 × 4.6 mm, 5 μm) and UV detection at 237 nm, confirming residual bromide area% below 0.5%. After chilling the quenched reaction mass to 0–5 °C and filtering through a 0.5 μm PTFE filter plate, the crude nitrile is recrystallized from isopropanol/water (70:30 v/v) to deliver febuxostat with a purity exceeding 99.8% by HPLC. The terminal dosage form manufactured from this intermediate is the 40 mg or 80 mg film-coated tablet, a urate-lowering therapy requiring compliance with ICH Q3C(R8) residual solvent limits (N,N-dimethylformamide ≤ 880 ppm) and ICH Q3D elemental impurity thresholds (palladium ≤ 10 μg/day).

What Drives the Selection of Pd-Catalyzed Cyanation Over Stoichiometric CuCN in API Manufacturing?

The copper(I) cyanide route, historically entrenched in fine chemical production for aryl bromide displacement, introduces a stoichiometric metal load that complicates waste-stream treatment under US EPA 40 CFR 261 hazardous waste classification and elevates the risk of residual copper in the active pharmaceutical ingredient beyond the ICH Q3D permitted daily exposure of 1300 μg/day. When CuCN is employed, the molar addition of the cyanating agent typically ranges from 1.2 to 1.5 equivalents relative to the ethyl 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate charge, and the reaction is conducted in sulfolane or N-methyl-2-pyrrolidone at 140–160 °C inside a 316L stainless-steel or nickel-alloy agitated vessel. Work-up demands filtration of copper bromide by-products through a 0.2 μm ceramic membrane at 80 °C, followed by chelating resin treatment (iminodiacetic acid-functionalized styrene-divinylbenzene) to scavenge dissolved Cu⁺/Cu²⁺ to below 5 ppm. The terminal product, febuxostat crude, consistently exhibits a copper content spike when this heterogeneous filtration experiences a pressure drop exceeding 1.5 bar, necessitating repeat resin passes. In contrast, the palladium-catalyzed method with zinc cyanide generates a soluble ZnBr₂ by-product, kept below the 13 mg/day oral PDE for zinc, and permits a homogeneous reaction profile amenable to continuous-flow processing. A tubular reactor with a 1.0 mm internal diameter PFA coil and a residence time of 15 minutes at 120 °C, as demonstrated on a 100 g·h⁻¹ pilot line, delivers a stead-state conversion of 99.3% with an 87% isolated yield after falling-film evaporation at 50 mbar and 95 °C.

Comparative Cyanation Parameters for the Bromo Intermediate
Method	Reagent (molar ratio)	Catalyst	Temperature Range	Isolated Purity (HPLC)	Key Regulatory Standard
Stoichiometric CuCN	CuCN (1.3 eq.)	None	150–155 °C	99.1–99.5%	ICH Q3D (Cu PDE), 40 CFR 261
Pd/Zn(CN)₂	Zn(CN)₂ (0.58 eq.)	Pd(PPh₃)₄ (1.0 mol%)	100–110 °C	99.8–99.9%	ICH Q3C (DMF), ICH Q3D (Pd, Zn)
Pd/K₄[Fe(CN)₆]	K₄[Fe(CN)₆]·3H₂O (0.23 eq.)	Pd(OAc)₂ + dppf (1.5 mol%)	120–125 °C	99.5–99.7%	ICH Q3D (Fe), USP <231> for heavy metals

Suzuki–Miyaura Coupling Substrate for Biaryl-Containing Drug Candidates

Exploiting the C-Br bond as a well-defined oxidative-addition handle, the ethyl 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate scaffold serves as a bench-stable coupling partner in the construction of biaryl libraries targeting phosphodiesterase and kinase inhibition pharmacophores. A typical parallel medicinal chemistry protocol adds the bromide at a 1.0 equivalent loading with respect to the boronic acid partner (1.05–1.2 equivalents) in a degassed mixture of 1,4-dioxane and aqueous 2 M K₂CO₃ (3:1 v/v), using [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2 mol%) under argon. The reaction is conducted in 10 mL microwave vials with septum-sealed caps, irradiated at 100 W to reach 110 °C for 45 minutes. Downstream processing involves filtration through a 0.45 μm syringe filter, evaporation on a Genevac HT-4X solvent evaporator at 40 °C, and purification via prep-HPLC (C18, 10 μm, 250 × 21.2 mm column) with a water/acetonitrile + 0.1% TFA gradient. The resulting 5-(biaryl)-thiazole-4-carboxylate esters are then subjected to ester hydrolysis in 1 M LiOH/1:1:1) at 25 °C for 12 hours, liberating the carboxylic acid terminal group for in vitro assay without decarboxylation, provided the pH during acidic work-up is held above 3.5. The end-product types are research-batch free acids and corresponding sodium salts submitted to OECD 423 acute oral toxicity screens and CYP450 inhibition panels in accordance with GLP principles.

When Bromine Serves as a Masking Group Prior to Late-Stage Functionalization

In a divergent synthesis strategy, the aryl bromide moiety is deliberately retained through a multi‑step sequence until the penultimate transformation, at which point it undergoes a lithium-halogen exchange to install electrophilic substituents incompatible with earlier intermediates. The ethyl 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate is first converted to its corresponding pinacolboronate ester via a Miyaura borylation (bis(pinacolato)diboron, 1.1 eq., PdCl₂(dppf)·CH₂Cl₂, 3 mol%, KOAc 3.0 eq., dioxane, 85 °C, 16 h). This boron intermediate, isolated as a crystalline solid after trituration with n-heptane, is then subjected to anhydrous hydrogen peroxide in acetic acid (30 wt% H₂O₂, 2.0 eq.) to yield the 3-hydroxy analogue—a critical scaffold for glucuronide metabolite synthesis required in FDA 21 CFR 58 compliant toxicology studies. During the borylation step, the reaction mixture must be maintained under strictly anaerobic conditions (dissolved oxygen < 0.5 ppm) and the reactor’s overhead space purged with argon at a rate of 0.5 reactor volumes per hour; failure to exclude oxygen results in homocoupling by-product reaching 8–12% area by HPLC. The hydroxy derivative is subsequently furnished to a cGMP facility for sequential coupling as a Phase II metabolite reference standard, authenticated against USP referee standards and quantified by LC-MS/MS with a lower limit of quantification of 0.1 ng·mL⁻¹.

Impurity Control Strategy for the Bromo Intermediate (Per ICH Q3A)
Impurity	Identification	Acceptance Criterion	Analytical Method	Regulatory Driver
Des-bromo analog	2-(4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate	≤ 0.10%	HPLC, USP <621>	ICH Q3A reporting threshold
Dibromo derivative	2-(3,5-dibromo-4-isobutoxyphenyl) analog	≤ 0.15%	UPLC-UV, C18, 2.1 mm × 100 mm, 1.7 μm	ICH Q3A identification threshold
Brominated succinimide	N-Bromosuccinimide residual	≤ 50 ppm	GC-FID, USP <467>	ICH Q3C
Palladium	Pd from coupling	≤ 10 μg/g	ICP-MS, USP <233>	ICH Q3D

Dehalogenation risk during the ester hydrolysis of ethyl 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate emerges when the reaction medium exceeds a pH of 12.5 or when the process temperature is maintained above 45 °C in the presence of hydroxide ion. Under tightly controlled conditions, a suspension of the ester (1.0 wt, corresponding to approximately 0.4 M) in tetrahydrofuran and water (5:1 v/v) is treated with lithium hydroxide monohydrate (1.3 equivalents) at 10–15 °C with a dosing rate not exceeding 0.3 mL·min⁻¹·kg⁻¹ of batch mass to prevent localized hot spots. Agitation is set to 250 rpm in a dished-bottom reactor equipped with temperature probes positioned at the vessel’s lowest point; the jacket supply temperature is limited to 5 °C differential from the process set point. After 14–18 hours, conversion to the lithium carboxylate exceeds 99.0%. Acidification with dilute hydrochloric acid to pH 4.5 ± 0.2 precipitates the free carboxylic acid, which is filtered, washed with chilled water (2 °C) until chloride is below 10 ppm, and dried in a vacuum tray dryer at 35 °C and 10 mbar for 24 hours. The resulting 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid, assay 99.5% by titration with 0.1 N tetrabutylammonium hydroxide, serves as a key building block for amide bond-forming reactions in combinatorial chemistry libraries. It is supplied in amber glass bottles under nitrogen to drug discovery units operating under ISO 17025 quality systems, with a certificate of analysis listing residual THF (< 720 ppm) and water (< 0.5%) according to USP <921>.

A high-temperature continuous bromination process in a static mixer reactor has been evaluated for the preparation of the immediate precursor to ethyl 2-(3-bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate on a metric-ton scale. The raw 4-isobutoxybenzaldehyde undergoes bromination with elemental bromine (1.02 equivalents) in acetic acid at 50 °C within a 3/16-inch diameter Teflon-lined static mixer with a residence time of 4.2 seconds, delivering mono-bromination selectivity of 98.7% and limiting the formation of the 3,5-dibromo impurity. The bromoaldehyde is then condensed with thiourea and ethyl 2-chloroacetoacetate in a one-pot Thiazolidine condensation conducted at 78 °C in ethanol, followed by azeotropic water removal at 120 mbar and distillation of the solvent to 15% residual volume. The crude thiazole ester is then crystallized from cyclohexane/methyl tert-butyl ether (4:1 v/v) using a seeded cooling profile from 50 °C to −5 °C at 0.2 °C·min⁻¹, affording a product with a differential scanning calorimetry onset melting point of 132.7 °C (DSC, ASTM E537). The avoidance of amine bases in any step prior to isolation is mandatory: trace tertiary amines catalyze a dehydrobromination pathway that generates the vinyl ether impurity detectable by LC-MS at m/z 362.1. This integrated route, compliant with ISO 14001 environmental management and OHSAS 18001 safety protocols, supplies the bromo intermediate to generic drug manufacturers filing Drug Master Files incorporating ICH M4Q Common Technical Document format.

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Certification & Compliance

Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales9@bouling-chem.com.

More Introduction

What Distinguishes the 3-Bromo-4-isobutoxy Substitution Pattern from Meta- or Para-Alternatives?

Ethyl 2-(3-Bromo-4-Isobutoxyphenyl)-4-Methyl-5-Thiazolecarboxylate presents a 1,2,3-trisubstituted phenyl scaffold in which the bromine atom resides *ortho* to the isobutoxy group and *meta* to the thiazole linkage. This substitution geometry imposes a calculated dihedral angle of approximately 34° between the phenyl ring and the thiazole plane, as estimated by gas-phase DFT optimization at the B3LYP/6-31G* level using Gaussian 16. In contrast, the common para-bromo analogue—Ethyl 2-(4-bromophenyl)-4-methyl-5-thiazolecarboxylate—adopts a near-planar ground-state conformation (dihedral <10°), maximizing π-overlap but reducing solubility in medium-polarity media. The ortho-bromo arrangement weakens the aryl–thiazole conjugation, red-shifting the UV absorption maximum from 292 nm (para-isomer) to 306 nm in acetonitrile, as recorded on a Shimadzu UV-2600 spectrophotometer. The isobutoxy substituent further accentuates these differences. Its branched alkyl architecture increases the calculated octanol–water partition coefficient (logP) by roughly +0.8 log units relative to the 4-methoxy congener—Ethyl 2-(3-bromo-4-methoxyphenyl)-4-methyl-5-thiazolecarboxylate—when computed via the consensus model embedded in Molecular Operating Environment (MOE) 2022.02. This translates into a predicted logD_7.4 of 3.9 ± 0.3, a value that falls within the optimal range for passive CNS permeation under the Wager criteria, whereas the methoxy derivative yields a logD_7.4 near 3.1. Steric shielding of the bromine by the adjacent isobutoxy group also retards oxidative addition in palladium-catalyzed couplings; kinetic profiling by in situ ReactIR monitoring (Mettler Toledo ReactIR 15) reveals an induction period of 3–5 minutes at 60°C before the Pd(0) insertion becomes measurable, compared to <1 minute for the 4-methoxy variant under identical conditions (Pd(OAc)₂, SPhos, K₃PO₄, THF/H₂O). This latency can be exploited in sequential one-pot transformations where differentiation of multiple aryl halides is required. Without a header, the next scenario opens directly: Samples received from pilot-scale campaigns (batch sizes 250–500 g) have been subjected to polymorph screening by differential scanning calorimetry (DSC) according to ASTM E794. A single endothermic melting event is consistently observed at 114–116 °C (onset), with no solid-solid transitions detected upon heating at 10 °C/min under nitrogen purge. X-ray powder diffraction (XRPD) patterns recorded on a Bruker D8 Advance diffractometer (Cu Kα, 40 kV, 40 mA) remain invariant across three independent lots, confirming the absence of concomitant polymorphism under standard isolation conditions. Stability under accelerated conditions (40°C/75% RH, open vial, 14 days) shows <0.3% degradation by HPLC area percent at 254 nm, with the sole degradant identified as the corresponding carboxylic acid arising from ester hydrolysis. The hydrolysis rate constant at pH 6.8 phosphate buffer and 37°C is 2.1 × 10⁻⁷ s⁻¹, indicating a shelf half-life exceeding 900 hours in neutral aqueous media.

Utilizing the Aryl Bromide Handle in Palladium-Catalyzed Cross-Coupling Protocols

The bromine substituent serves as a versatile exit vector for C–C and C–heteroatom bond construction. Suzuki–Miyaura coupling with (4-fluorophenyl)boronic acid proceeds to >85% conversion within 2 hours at 80°C using 1 mol% Pd(PPh₃)₄, 2 eq Na₂CO₃ in degassed 1,4-dioxane/water (3:1 v/v). The isolated yield after flash chromatography (Biotage Isolera One, Sfar C18 Duo 30 µm column, gradient 5→95% MeCN in water over 15 CV) averages 78% across triplicate runs, with residual palladium content measured by ICP-MS per USP <233> falling below 5 ppm after a single treatment with QuadraSil MP scavenger. The steric bulk of the isobutoxy group suppresses homo-coupling of the boronic acid; the biphenyl impurity remains <1.5 area% when the reaction is sparged with argon for 15 minutes prior to catalyst introduction. Buchwald–Hartwig amination with morpholine under the catalytic system Pd₂(dba)₃ (0.5 mol%) / Xantphos (1.0 mol%) / NaOtBu (1.4 eq) in toluene at 100°C delivers the corresponding 3-morpholino-4-isobutoxyphenyl adduct in 73% yield. Importantly, chemoselectivity for the aryl bromide over the thiazole C–H positions is complete; no regioisomeric amination products are detected by UPLC-MS (Waters ACQUITY H-Class, CORTECS C18+ column, 1.6 µm, 2.1 × 50 mm). The electron-deficient nature of the thiazole ring, with a calculated LUMO energy of -1.82 eV (B3LYP/6-31G*), makes it resistant to direct nucleophilic aromatic substitution under these conditions, a key advantage over pyridine-containing scaffolds where competing C–N bond formation is frequently observed.

When Elevating Coupling Temperatures Above 100°C Necessitates Solvent Switching

The ethyl ester functionality imposes a thermal ceiling. Thermogravimetric analysis (TGA, ASTM E2550) on a TA Instruments Q5000 IR shows the onset of mass loss at 152°C (heating rate 10 °C/min, N₂ atmosphere), attributed to decarboxylative decomposition. Differential scanning calorimetry confirms that no exothermic events occur below 140°C. Therefore, coupling reactions requiring temperatures above 100°C—for example, reactions of deactivated aryl chlorides—must be conducted in high-boiling solvents while keeping the pot temperature below 130°C. N,N-Dimethylacetamide (DMAc, bp 165°C) and sulfolane (bp 285°C) have been screened; in sulfolane at 125°C, the rate of decomposition increases to ~2% per 8 hours, as tracked by periodic HPLC sampling. Consequently, continuous flow processing in a Vapourtec R-Series reactor (PEEK coil, 10 mL internal volume, 0.5 mL/min flow rate, back-pressure regulator set to 7 bar) enabled a residence time of 12 minutes at 130°C while limiting degradation to <0.5%. This protocol successfully delivered the Negishi coupling product with 2-thienylzinc bromide in 81% isolated yield after evaporation and trituration with heptane. Without a header, this scenario discusses storage and incompatibilities: Long-term storage trials at -20°C under argon (Aldrich Sure/Seal packaging) demonstrate no detectable degradation after 24 months by HPLC. Exposure to ambient light should be minimized; photolytic debromination has been observed in acetonitrile solution when irradiated with a 254 nm mercury lamp (UVP Pen-Ray, 5.5 mW/cm²), generating ~4% of the debrominated des-bromo analogue within 6 hours. Amber borosilicate glassware is recommended for all solution-phase manipulations. The compound is incompatible with strong nucleophiles such as alkoxide bases; a rapid exotherm and formation of multiple colored by-products occur upon addition of sodium methoxide in methanol at 0°C. Transesterification with alcohols in the presence of titanium(IV) isopropoxide can replace the ethyl ester with higher alkyl chains, but reaction times extend to 48 hours at reflux for the isopropyl ester derivative.

Chromatographic Purification and Residual Metal Specifications

The principal process-related impurities routinely monitored include the des-bromo analogue (systematically generated via hydrogenolysis during synthesis), the carboxylic acid hydrolytic degradant, and the Suzuki-derived homocoupling dimer. A stability-indicating HPLC method per USP <621> achieves baseline resolution (Rs > 2.0) between the main peak and all identified impurities. Typical method parameters: column – Phenomenex Kinetex C18 (150 × 4.6 mm, 5 µm); mobile phase A – 0.1% trifluoroacetic acid in water; mobile phase B – 0.1% TFA in acetonitrile; gradient – 30% B to 90% B over 20 minutes; flow rate – 1.0 mL/min; column temperature – 30°C; detection – UV at 254 nm. Under these conditions, the relative retention time (RRT) of the des-bromo impurity is 0.85, the carboxylic acid impurity RRT 0.62, and the homocoupling dimer RRT 1.42. Quantification is against external standard curves with correlation coefficients ≥ 0.9995 over a range of 0.05% to 5.0% of the target concentration.

Compound	Substituent Pattern	Predicted logD₇.₄	Observed Melting Range (°C)	Typical Purity (HPLC, 254 nm)
Ethyl 2-(3-Bromo-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate	3-Br, 4-OiBu	3.9 ± 0.3	114–116	>98.5%
Ethyl 2-(4-bromophenyl)-4-methyl-5-thiazolecarboxylate	4-Br	2.8 ± 0.2	128–131	>98.0%
Ethyl 2-(3-bromo-4-methoxyphenyl)-4-methyl-5-thiazolecarboxylate	3-Br, 4-OMe	3.1 ± 0.2	107–109	>98.0%

Residual metals are controlled to align with the ICH Q3D guideline for elemental impurities in pharmaceutical products intended for oral administration. Palladium is the metal of primary concern. A post-synthetic purification sequence consisting of (i) slug-flow extraction with 10% w/v aqueous L-cysteine at 50°C, (ii) filtration through a pad of Celite 545, and (iii) crystallization from ethanol/water (3:1 v/v) consistently reduces Pd levels from initial values of 200–500 ppm (post-reaction) to <5 ppm. Iron and copper content are typically <10 ppm each, as determined by an Agilent 7900 ICP-MS system operating in helium collision mode. A section without a header presents further comparative biological relevance: In preliminary kinase selectivity panels, the thiazolecarboxylate core has been elaborated into potent inhibitors of Pim-1 kinase when the bromine is replaced with heteroaryl moieties via Suzuki coupling. The presence of the isobutoxy group enhances cellular potency relative to the methoxy analogue by a factor of 3–5 (IC₅₀ shift) in K562 cell proliferation assays, a finding correlated with increased intracellular accumulation measured by LC-MS/MS. Nevertheless, oral bioavailability in rodent models remains limited (F < 15% in Sprague-Dawley rats at 10 mg/kg) due to high first-pass metabolism of the ester function, necessitating prodrug strategies or ester bioisostere replacement. No formal GLP toxicology studies have been disclosed for this exact intermediate; handlers should observe standard precautions for halogenated aromatics and thiazoles, including the use of nitrile gloves (Ansell Sol-Vex, breakthrough time > 480 minutes for acetone) and fume hood containment with a face velocity of 0.5 m/s. Waste streams containing the compound must be incinerated at ≥ 1000°C with a residence time of ≥ 2 seconds, per local environmental regulations modeled on EU Directive 2010/75/EU.