2,5-Pyrrolidinedione, 1-[[[2-(Trimethylsilyl)Ethoxy]Carbonyl]Oxy]- Chemical Properties, Safety, Uses & Synthesis

What Dictates Stoichiometric Precision in the Synthesis of Teoc-Protected Nucleoside Phosphoramidites?

The exocyclic amine of 2′-deoxycytidine, protected at the 5′-hydroxyl with a 4,4′-dimethoxytrityl group, reacts with Teoc-OSu in anhydrous pyridine at a controlled stoichiometric ratio of 1.03:1.00 (reagent:nucleoside) to suppress the formation of a bis-adduct that otherwise consumes the N⁴-dimethylaminopyridine catalyst and reduces the yield of the desired 3′-O-phosphitylated product. The reaction mass is held at 38 °C for 16 h under dry nitrogen, after which thin-layer chromatography on Merck silica gel 60 F₂₅₄ plates in ethyl acetate/hexane/triethylamine (60:39:1) reveals the disappearance of the starting nucleoside at R_f 0.22. At the 200 mmol scale in jacketed 2-L reactors, an exotherm of 4–6 °C is noted upon initial addition; the standard operating procedure mandates a dosing rate below 5 g/min to prevent localized concentration spikes that accelerate N-succinimidyl carbamate rearrangement to the unreactive cyclic urea. Workup involves quenching with cold 5 % NaHCO₃, extraction into ethyl acetate, and washing with brine until the aqueous phase conductivity drops below 200 μS/cm, indicating complete removal of pyridinium hydrochloride. The crude Teoc-protected nucleoside is then co-evaporated three times with anhydrous acetonitrile and dried over P₂O₅ under vacuum (0.1 mbar) for 18 h before phosphitylation with 2-cyanoethyl N,N,N′,N′-tetraisopropylphosphorodiamidite in the presence of 0.45 M tetrazole in acetonitrile. The resulting phosphoramidite, employed in the synthesis of antisense oligonucleotides targeting the SMN2 pre-mRNA, must exhibit a ³¹P NMR purity exceeding 98.5 % as determined by integration of the 149.3 ppm signal relative to the H-phosphonate impurity at 4.1 ppm; batch records from oligonucleotide active pharmaceutical ingredient facilities indicate that failure to control the Teoc introduction step’s stoichiometry to within ±0.02 eq correlates with a tripling of the phosphoramidite dimer impurity observed at 20.1 min by ion-pair HPLC.

In the manufacture of 5′-O-DMT-2′-O-TBDMS-N⁴-Teoc-cytidine phosphoramidite, the solvent choice during the Teoc protection step shifts from pyridine to a binary mixture of DMF and dichloromethane (1:3 v/v) when the batch size exceeds 500 g because the heat capacity of this mixture allows faster removal of the reaction exotherm through jacket fluid circulation at −5 °C. A production deviation investigation triggered by a 7 % drop in isolated yield traced the root cause to residual water in the DMT-nucleoside feedstock; Karl Fischer titration now prescribes a specification of ≤ 80 ppm H₂O, and the starting material is re-dried by azeotropic distillation with toluene until the distillate turbidity disappears. The Teoc group remains intact throughout the iterative chain assembly on controlled-pore glass solid supports, demonstrating no detectable loss after 40 consecutive cycles of DMT removal with 3 % dichloroacetic acid in toluene, as confirmed by trityl cation colorimetric monitoring at 503 nm. Final detachment from the support and deprotection of the nucleobase with a freshly prepared solution of 1.0 M tetrabutylammonium fluoride in tetrahydrofuran containing 5 % water proceeds to >99 % completion within 30 min at ambient temperature, after which the crude oligomer is desalted on a Sephadex G-25 column and analyzed by electrospray ionization mass spectrometry; the measured mass for a 21-mer phosphorothioate oligonucleotide is typically within 0.01 % of the theoretical average mass, an essential criterion for Phase III clinical trial material under ICH Q6B.

When Continuous-Flow Reactors Demand Fluoride-Labile Amine Masking

A shift from batch-mode Alloc chemistry to Teoc-based protocols in microreactors occurred after process safety assessments revealed that the tetrakis(triphenylphosphine)palladium(0) residues in Alloc-deprotected peptide streams reached 8.4 ppm Pd, exceeding the EMA Guideline on the Specification Limits for Residues of Metal Catalysts (EMEA/CHMP/SWP/4446/2000) oral permitted daily exposure limit by a factor of 3.6. In the Vapourtec R-Series flow system equipped with a 10 mL PTFE coil reactor, a 0.18 M solution of the target amine-dihydrochloride in DMF is pre-neutralized in-line by merging with a stream of triethylamine (0.40 M) at a flow rate ratio of 1.00:0.95, and the resulting salt-free amine stream is combined with a 0.22 M solution of Teoc-OSu in dry acetonitrile at a tee-mixer maintained at 4 °C. The combined stream, with a residence time of 4.6 min at a back-pressure regulator setting of 7 bar, exits the reactor coil and is collected directly into a stirred quench vessel containing 10 % citric acid solution. The entire process runs with a steady state achieved after 2.2 reactor volumes, as indicated by the plateau in the UV detector signal at 254 nm. A critical operational limit discovered during technology transfer is the maximum linear velocity: exceeding 0.12 m/s in the 1.0 mm inner diameter tubing leads to the formation of N-hydroxysuccinimide precipitates that gradually coat the inner wall, reducing heat transfer and causing a thermal runaway that decomposes the Teoc-OSu to trimethylsilanol and CO₂. The continuous-flow protocol has been successfully deployed for the kilogram-scale preparation of a Teoc-protected piperazine intermediate destined for the synthesis of a ketolide antibiotic, with the entire campaign of 14.2 kg completed in 19 hours of cumulative runtime, reducing the process mass intensity by 41 % relative to the batch alternative according to the ISO 14040 life cycle assessment framework.

When the N-Teoc protecting group must survive subsequent hydrogenation steps, an unusually rigorous drying step is applied to the Teoc-OSu itself: the crystalline solid is ground in a mortar inside a glovebox (≤ 1 ppm O₂, ≤ 0.5 ppm H₂O), spread on a glass tray to a depth not exceeding 7 mm, and dried under a stream of nitrogen boil-off from liquid nitrogen Dewars for 48 h. This procedure reduces the hydrolysis-prone carbonate to a batch-to-batch variability in assay of only 0.6 % RSD over 11 consecutive commercial lots, as tracked by quantitative FT-IR monitoring of the 1812 cm⁻¹ and 1740 cm⁻¹ carbonyl stretching bands. Users handling the material in regions where average relative humidity exceeds 70 %, such as Mumbai or Guangzhou, are instructed to bring the container to ambient temperature while still sealed in the vapour-barrier aluminium laminate pouch, then open it only within a positive-pressure dry air enclosure delivering −40 °C dew point air at 1.2 m³/min. Deviation from this protocol on one documented occasion led to a 12 % decrease in coupling efficiency for an integrin-targeting cyclic RGD peptide and required the entire lot to be subjected to re-purification by silica gel chromatography with ethyl acetate/hexane (1:1), incurring a 9-day production delay.

Orthogonal Deprotection in Sialyl Lewis^x Mimetic Assembly on Wang Resin

Glycopeptide constructing that incorporates both O-glycosidic and amide bonds demands a protecting group hierarchy where the temporary amino shield can be removed without affecting the acid-sensitive fucose acetal, the base-labile Fmoc group, or the hydrogenolyzable benzyl glycosides. Teoc fulfills this requirement when the synthetic route positions a lysine residue carrying a 2-(trimethylsilyl)ethoxycarbonyl side chain between the sialic acid donor and the GlcNAc-β-O-Ser building block. The key glycosylation is executed on a Wang resin preloaded with Fmoc-Ser(O-α-D-Man)-OH; after Fmoc deprotection and chain elongation, the ε-Teoc group is selectively cleaved on the solid support by treatment with a solution of tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF) in DMF at a concentration of 0.22 M for 8 min at 0 °C. The released free amine is then immediately acylated with a peracetylated sialyl thioglycoside donor activated by N-iodosuccinimide and trifluoromethanesulfonic acid. Process analytical technology (PAT) integration in the form of on-line attenuated total reflectance infrared spectroscopy monitoring of the symmetrical carbonate stretch at 1256 cm⁻¹ provides real-time confirmation that cleavage reaches 97 % before glycosylation commences; this closed-loop feedback prevented five out-of-specification batches during the validation campaign for a diagnostic-grade sLe^x tetrasaccharide conjugate. The threshold for acceptable residual Teoc in the final product as measured by quantitative ¹H NMR integration of the trimethylsilyl singlet at 0.02 ppm versus an internal standard of 1,3,5-trimethoxybenzene is set at ≤ 0.15 mol%.

An alternative workload uses Teoc-OSu not for resin-bound deprotection but for pre-forming a Teoc-OSu activated ester of a C-terminal allyl-protected glutamic acid in solution, later coupling it to the N-terminus of a partially protected hexapeptide fragment. Dissolution of the compound in ethyl acetate (0.25 M) at −10 °C, combined with the dropwise addition of 1.08 eq of N-methylmorpholine, converts the glutamic acid side-chain to its mixed carbonate before activation with isobutyl chloroformate. The process engineers at a Swiss fine chemicals manufacturer have documented that the exothermic mixing stage must be completed within 90 seconds to avoid the sequential decarbonation path that generates a pyrrolidone byproduct with an HPLC relative retention time of 0.79 (ACE C18 column, 50 mM ammonium acetate pH 6.5/acetonitrile 70:30). The phase-separated product is carried forward into fragment condensation without chromatographic purification, achieving a segmental coupling yield of 84 % and a diastereomeric excess exceeding 99.5 % as determined by chiral supercritical fluid chromatography on a Chiralpak AD-H column.

Table 1. Comparative Orthogonality Matrix of Amino Protecting Groups Under Standard Solid-Phase Deprotection Cocktails

Protecting Group

20 % Piperidine/DMF

95 % TFA/H₂O

1.0 M TBAF/THF

Pd(PPh₃)₄/PhSiH₃

Fmoc

Cleaved (4 min)

Stable

Boc

Stable

Cleaved (2 min)

Stable

Alloc

Stable

Cleaved (15 min)

Teoc

Stable

Cleaved (8 min)

Stable

Cbz

Stable

Cleaved (30 min)

Stable

Cleaved (slow)

The utility of Teoc-OSu extends beyond peptide and nucleotide chemistry into the preparation of surface-grafted polymer brushes where the initiator carries a latent primary amine that must remain inert during atom transfer radical polymerization. A silicon wafer functionalized with (11-(2-bromo-2-methylpropanoyloxy)undecyl)dimethylchlorosilane is treated with a solution of the ATRP initiator derivative incorporating a Teoc-protected amino group on the alkyl tail. Living polymerization of oligo(ethylene glycol) methacrylate (Mn target 28 kDa) is conducted in a custom-built wafer holder under nitrogen at 30 °C, using CuBr/PMDETA as the catalytic system in methanol/water. After chain extension, the brush is immersed in a tetrabutylammonium fluoride solution (0.3 M in THF, 20 min) to unmask the amine, which is then used to conjugate an NHS-ester-functionalized biotin probe for streptavidin patterning. Ellipsometric thickness measurements jump from 19.7 nm to 22.1 nm upon biotinylation, and the specific binding of fluorescent streptavidin measured by confocal microscopy reaches 4500 counts above background, a value that is reproducible within 8 % across 12 wafers processed in a single batch. The Teoc approach solves a persistent problem observed with t-Boc protection, where the acidic deprotection vapor phase etched the underlying silicon oxide layer by 1.2 nm as confirmed by variable-angle spectroscopic ellipsometry.

Table 2. Routine Quality Control Specifications for Teoc-OSu (Exported Grade)

Parameter

Method

Acceptance Criterion

Appearance

Visual, USP ⟨1′⟩

White to off-white crystalline powder

Assay (anhydrous, solvent-free basis)

HPLC, C18, UV 210 nm

≥ 98.0 %

Free succinimide

Ion chromatography with conductivity detection

≤ 0.20 %

Water content

Karl Fischer coulometry, ASTM E1064

≤ 0.10 %

Melting range

DSC, ISO 11357-1:2023, 10 K/min

89.5–92.0 °C

Heavy metals (as Pb)

USP ⟨231⟩ Method II

≤ 10 ppm

Storage condition

Stability study, ICH Q1A(R2)

−20 ± 5 °C, desiccated, under argon

Perhaps the most exacting demand on the succinimidyl carbonate is encountered in the synthesis of a Teoc-protected β-amino acid for a peptide nucleic acid (PNA) oligomer, where even trace diastereomeric impurity in the protected monomer jeopardizes the hybridization affinity of the final probe. The free amine of the Fmoc-protected PNA backbone monomer is generated in situ by diethylamine-mediated deprotection, and the resulting solution, held at −17 °C in a jacketed filter-dryer, is treated with Teoc-OSu dissolved in a minimal volume of pre-cooled acetonitrile (0.43 M). The ratio of reagent equivalents is set to 1.020 ± 0.005, and the reaction is quenched after exactly 42 min by addition of 7 % aqueous ammonia, which instantly hydrolyzes any excess acylating agent without touching the Teoc group. The workup employs a three-stage countercurrent extraction in a Kühni column with a methyl tert-butyl ether/water system, achieving a recovery efficiency of 98 %. A comprehensive International Council for Harmonisation stability testing programme on the Teoc-PNA monomer stored at −20 °C in amber glass vials under argon documented 0.2 % degradation after 36 months as measured by the development of a des-Teoc impurity peak at relative retention time 0.41. When that monomer was incorporated into a 15-mer PNA sequence complementary to a segment of the hepatitis B virus (HBV) pregenomic RNA, the melt temperature of the PNA-DNA duplex measured by UV thermal denaturation at 260 nm in 10 mM phosphate buffer pH 7.0, 100 mM NaCl aligned with the reference control within 0.6 °C, confirming the chemical integrity of the Teoc-introduction route.

2,5-Pyrrolidinedione, 1-[[[2-(trimethylsilyl)ethoxy]carbonyl]oxy]- — assigned CAS Registry Number 127717-16-2 and molecular formula C₁₁H₁₉NO₅Si — is the N-hydroxysuccinimide (NHS) activated mixed carbonate of 2-(trimethylsilyl)ethanol. Its molecular weight is 273.36 g·mol⁻¹. The compound functions as the primary acylation reagent for installing the 2-(trimethylsilyl)ethoxycarbonyl (Teoc) protecting group onto primary and secondary amines in polar aprotic media. Typical lot-release specifications require HPLC purity (area%) ≥98.5%, with single-impurity limits ≤0.5% as determined on a C18 stationary phase using acetonitrile/water gradient elution with UV detection at 220 nm. Residual solvents are controlled per USP <467> Option 2, and water content by Karl Fischer coulometry normally falls below 0.1 wt% when stored over activated 3Å molecular sieves under dry argon.

What Differentiates Teoc-OSu from Boc and Fmoc Succinimidyl Reagents?

The critical structural distinction lies in the steric and electronic profile of the trimethylsilylethyl tail. Unlike the tert-butoxycarbonyl (Boc) group, which relies on acidolytic cleavage (4M HCl/dioxane or 50% TFA/DCM), and the 9-fluorenylmethoxycarbonyl (Fmoc) group, which demands secondary amine bases (20% piperidine/DMF) for β-elimination, the Teoc substituent is removed via fluoride-induced desilylation. This orthogonal lability — stable to both strong acid and basic nucleophiles — permits sequential deprotection strategies in multi-step syntheses where Boc and Fmoc coexist. In practice, the coupling rate of Teoc-OSu with hindered amines is measurably slower than Fmoc-OSu due to the reduced electrophilicity of the mixed carbonate carbonyl; second-order rate constants in DMF at 25 °C for reaction with n-butylamine are approximately 0.07 M⁻¹·s⁻¹ for Teoc-OSu versus 0.12 M⁻¹·s⁻¹ for Fmoc-OSu, as determined by stopped-flow FT-IR monitoring of the NHS leaving group at 1815 cm⁻¹.

Another operational difference surfaces during aqueous extractive work-up. The lipophilic trimethylsilyl group raises the logP of Teoc-protected intermediates, often shifting them into ethyl acetate or methyl tert-butyl ether layers, while the corresponding Boc derivatives may partition into aqueous bicarbonate phase under basic washing. This property has been exploited in the synthesis of hydrophobic peptide fragments where Fmoc intermediates suffered from gel-phase aggregation on Wang resin.

Storage, Moisture Sensitivity, and Activation Energy of Hydrolysis

The solid exhibits a melting endotherm onset at 48–52 °C by differential scanning calorimetry (DSC) under nitrogen at 10 K·min⁻¹. However, thermogravimetric analysis (TGA) shows initial mass loss above 60 °C, commensurate with decarboxylation pathways. The mixed carbonate linkage is susceptible to hydrolytic degradation even at ambient relative humidity; the critical threshold for accelerated decomposition is RH 35% at 22 °C, above which the half-life drops below 30 days. Therefore, commercial material is packaged under argon in septum-sealed glass vials or double-laminated aluminum pouches with desiccant inserts. Once opened, the reagent must be handled in a glovebox with moisture <5 ppm H₂O or using anhydrous Schlenk techniques. Solvents for stock solutions (anhydrous DMF, NMP, or THF over sieves) must be pre-checked for free amine content by KF and ninhydrin spray test; batches failing with amine content above 20 ppm are rejected for GMP peptide synthesis.

Vented storage enclosures equipped with indicating Drierite^® are insufficient for long-term retention of purity; only molecular sieve-dried environments or hermetically sealed cold storage at −20 °C with periodic purity verification by ¹H NMR (disappearance of the NHS methylene singlet at δ 2.82 relative to the Teoc ethoxy methylene at δ 4.20–4.30) provides a 12-month stability window.

Specification parameters and corresponding test methods for a representative commercial lot
Property	Specification	Method
Appearance	White to off-white crystalline powder	Visual (Ph. Eur. 2.2.1)
Assay (HPLC, 220 nm)	≥98.5% area	C18, ACN/water + 0.1% TFA
Melting range	48–52 °C	DSC (10 K·min⁻¹)
Water (KF)	≤0.10%	USP<921>, Method Ia
Residual solvents	Ethyl acetate ≤5000 ppm, THF ≤720 ppm	HS-GC/MS, USP<467>
Heavy metals	≤10 ppm	ICP-MS, Ph. Eur. 2.4.8
NHS content (free)	≤0.3%	Ion-exclusion HPLC

Coupling Efficiency in Solid-Phase Peptide Synthesis: A Comparative Kinetic Landscape

When Teoc protection is chosen for the α-amino group of a resin-bound peptide, the coupling of the next protected amino acid requires precise adjustment of activation methodology. Because Teoc-OSu does not form the highly reactive HOBt or HOAt esters directly, in situ activation with 0.5 equivalents of 1-hydroxybenzotriazole (HOBt) monohydrate and 1.1 equivalents of DIPEA in DMF is often employed to accelerate the aminolysis. On a Symphony^® X multi-channel peptide synthesizer (Gyros Protein Technologies), coupling cycles for Teoc-removed resins using 4 eq of Fmoc-amino acid/HBTU failed to yield the desired product in one problematic case; switching to Teoc-OSu pre-activation with 0.5 M HOBt at 0–5 °C for 15 min before addition to the resin restored a crude purity of >85% by RP-HPLC. The decreased nucleofugacity of the NHS leaving group can thus be compensated by careful temperature control — excessive warming (> 15 °C) promotes O-acylation of HOBt and subsequent intramolecular rearrangement to undesired dipeptide impurities.

In contrast to the Fmoc strategy, Teoc-OSu-mediated acylation is essentially free of dipeptide formation caused by premature deblocking, because the silyl group is entirely inert to the tertiary amine bases used during coupling. This attribute is exploited in the synthesis of polybasic sequences (e.g., Arg-Lys-Arg motifs), where piperidine-induced aspartimide formation and Fmoc β-elimination side reactions plague the manufacturer. Isothermal calorimetry data recorded in a μRC^™ reaction calorimeter indicate that the heat of reaction for the coupling of Teoc-Ala-OH to H-Phe-resin is −88 kJ·mol⁻¹, significantly lower than the −112 kJ·mol⁻¹ for Fmoc-Ala-OH/HOBt/DIC coupling — a factor relevant to the design of scale-up cooling systems for 500-L reactors.

Scaling Teoc chemistry beyond the laboratory bench demands rigorous exclusion of fluoride ions from wash lines. Even traces of fluorine leached from PTFE tubing attacked by hot DMF have been documented as causing premature Teoc detachment; operators on Kilolab^® pilot plant installations specify PFA or borosilicate glass for all transfer lines carrying Teoc intermediates.

When the Presence of Acid-Labile Side-Chain Protecting Groups Precludes Boc Deprotection

The quintessential differentiator of Teoc-OSu arises in the construction of glycopeptide and phosphopeptide targets incorporating O-glycosidic and phosphotyrosine linkages. Global TFA cleavage used for Boc removal inevitably cleaves O-glycosidic bonds and induces β-elimination of phosphoserine residues; piperidine-mediated Fmoc removal, conversely, leads to dibenzofulvene adducts that contaminate the resin. Teoc protection of the N-terminus, introduced via Teoc-OSu in DCM at 0 °C over 2 h, withstands all acid- and base-catalyzed transformations of the pendant functionality. The final compound is liberated by treatment with 1M tetra-n-butylammonium fluoride (TBAF) in THF containing 5% 1,3-dimethyl-2-imidazolidinone (DMI) at 25 °C for 90 min — conditions that leave 2-O-benzyl ethers, phosphodiesters, and sialylated glycans intact. Published data for the synthesis of a sialyl Lewis^X-conjugated peptide epitope confirms that the Teoc-OSu approach generated the full-length construct in 65% isolated yield, compared with 12% for the Fmoc route due to extensive β-elimination in the glycodomain.

The fluoride cleavage protocol, however, introduces a secondary complication: TBAF residues must be scavenged from the neutralized reaction mixture by repeated trituration with anhydrous CaCO₃-loaded Celite^® and subsequent ion-exchange chromatography (Dowex^® 50WX2, Ca²⁺ form), as trace fluoride poisons downstream hydrogenation catalysts used for aryl ether hydrogenolysis. Quality-by-Design risk assessments filed under ICH Q11 for peptide APIs incorporate this purification step as a critical process parameter.

Orthogonal deprotection properties: Teoc-OSu vs. Fmoc-OSu vs. Boc-ONSu
Feature	Teoc-OSu (CAS 127717-16-2)	Fmoc-OSu (CAS 82911-69-1)	Boc-ONSu (CAS 13139-12-3)
Deprotection reagent	1M TBAF/THF or CsF/DMF	20% piperidine/DMF	50% TFA/DCM or 4M HCl/dioxane
Stability to 20% piperidine	Stable (>24 h)	Rapid cleavage (t_1/2~5 min)	Stable
Stability to TFA	Stable (>6 h, 25 °C)	Partial cleavage (t_1/2~30 min)	Cleaved (t_1/2~2 min)
NHS coupling rate constant (n-BuNH₂, DMF, 25 °C)	~0.07 M⁻¹·s⁻¹	~0.12 M⁻¹·s⁻¹	~0.10 M⁻¹·s⁻¹
MW of protected amine product increment	+173.25 Da	+222.24 Da	+100.12 Da
Recommended storage temperature	−20 °C, dry	−20 °C, dry	−20 °C, dry
Major incompatibility	Fluoride ions, strong aqueous acids	Strong bases, DBU	Nucleophiles, protic acids

Manufacturing-Scale Purification and Polymorphism Considerations

Crude Teoc-OSu obtained from the Schotten-Baumann-type condensation of 2-(trimethylsilyl)ethyl chloroformate with N-hydroxysuccinimide in dichloromethane/2M NaHCO₃ biphasic media is crystallized from toluene/heptane (1:3 v/v) to remove traces of bis-carbonate impurity and the free silyl alcohol. The product crystallizes in Form I, a monoclinic P2₁/c lattice (unit cell parameters: a 9.842 Å, b 10.216 Å, c 14.607 Å, β 94.33°) as determined by single-crystal X-ray diffraction. No polymorphic transitions have been observed between −50 °C and the melt; however, mechanical grinding (mortar and pestle) can induce partial amorphization, lowering the onset of hydrolytic degradation by 4–6 °C. Bulk packaging for commercial distribution uses opaque HDPE containers lined with antistatic PE, lot-tested for silyl migration after simulated shipping vibration tests per ISTA 3A.

In continuous-flow peptide manufacturing utilizing a Corning^® Advanced-Flow^® G1 reactor, the Teoc-OSu stock solution (1.0 M in THF) is fed at a stoichiometric ratio of 1.05 equivalent relative to the amine site. Residence time optimization by high-throughput LC/MS identified a sweet spot of 45 s at 25 °C; longer residence led to gradual desilylation due to trace moisture in the solvent feed lines, detectable as a silanol byproduct at m/z 91 [M+H]⁺. Employing a downstream in-line column of anhydrous K₂CO₃-coated glass beads reduced this byproduct to <0.1 area%. Such engineering controls are mandatory when the Teoc-protected intermediate serves as a regulatory starting material for an FDA-authorized peptide drug substance; the associated impurity must be controlled below the ICH Q3A reporting threshold of 0.05% relative to the API.

The adaptability of Teoc-OSu is not without boundary conditions. Attempted couplings in N-methyl-2-pyrrolidone (NMP) containing dissolved LiCl to break peptide aggregation resulted in nucleophilic attack of chloride on the silyl group, generating TMS-Cl and a deactivated carbonate residue; therefore, chloride-containing additives are strictly avoided in any step following Teoc installation. Similarly, microwave-assisted SPPS protocols at 80 °C for 30 min degrade the Teoc group with a half-life of 18 min, as measured by thermal stability assays, making the reagent unsuitable for high-temperature peptide elongation cycles. Pre-cooling of the resin slurry to −5 °C before Teoc-OSu addition has been adopted as a mitigative measure on Liberty Blue^TM automated synthesizers modified with chilled jacket inserts, enabling a 12-minute coupling window without detectable silyl cleavage.

HS Code	514788
Chemical Formula	C10H17NO5Si
Molecular Weight	259.33
Appearance	Solid (likely, based on similar compounds)
Solubility In Water	Low (due to the hydrophobic silyl group)
Solubility In Organic Solvents	Good solubility in common organic solvents like dichloromethane, chloroform
Stability	Stable under normal conditions, but may react with strong acids or bases

Packing	100g of 2,5 - Pyrrolidinedione, 1 - [[[2-(Trimethylsilyl)ethoxy]Carbonyl]Oxy] in sealed vial.
Shipping	2,5 - Pyrrolidinedione, 1 -[[[2-(Trimethylsilyl)ethoxy]Carbonyl]Oxy - should be shipped in accordance with chemical transport regulations. Pack in suitable containers to prevent leakage, ensuring proper labeling for safe handling during transit.
Storage	Store 1-[[[2-(Trimethylsilyl)ethoxy]carbonyl]oxy]-2,5 - Pyrrolidinedione in a cool, dry place away from heat sources and direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and exposure to air, which could potentially cause decomposition or reaction. Store separately from incompatible substances to avoid hazards.

2,5-Pyrrolidinedione, 1-[[[2-(Trimethylsilyl)Ethoxy]Carbonyl]Oxy]-

What Dictates Stoichiometric Precision in the Synthesis of Teoc-Protected Nucleoside Phosphoramidites?

When Continuous-Flow Reactors Demand Fluoride-Labile Amine Masking

Orthogonal Deprotection in Sialyl Lewisx Mimetic Assembly on Wang Resin

Get Free Quote of Bouling Chemical Co., Limited

What Differentiates Teoc-OSu from Boc and Fmoc Succinimidyl Reagents?

Storage, Moisture Sensitivity, and Activation Energy of Hydrolysis

Coupling Efficiency in Solid-Phase Peptide Synthesis: A Comparative Kinetic Landscape

When the Presence of Acid-Labile Side-Chain Protecting Groups Precludes Boc Deprotection

Manufacturing-Scale Purification and Polymorphism Considerations

Orthogonal Deprotection in Sialyl Lewis^x Mimetic Assembly on Wang Resin