| HS Code | 775985 |
| Product Name | L-Lysine Methyl Ester Hydrochloride |
| Chemical Name | L-Lysine methyl ester dihydrochloride |
| Iupac Name | Methyl (2S)-2,6-diaminohexanoate dihydrochloride |
| Cas Number | 26348-70-9 |
| Molecular Formula | C7H16N2O2·2HCl |
| Molecular Weight | 233.14 g/mol |
| Appearance | White to off-white crystalline powder |
| Melting Point | 216-220 °C (dec) |
| Optical Rotation | [α]20/D = +16.5°, c = 2 in water |
| Solubility | Soluble in water, methanol, ethanol; sparingly soluble in organic solvents |
| Purity | ≥98% |
| Storage Conditions | Store under inert atmosphere at 2-8°C, protected from moisture |
| Sensitivity | Hygroscopic |
| Smiles | COC(=O)[C@@H](N)CCCCN.Cl.Cl |
| Inchi | InChI=1S/C7H16N2O2.2ClH/c1-11-7(10)6(9)4-2-3-5-8/h6H,2-5,8-9H2,1H3;2*1H/t6-;/m0./s1 |
As an accredited L-Lysine Methyl Ester Hydrochloride factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | L-Lysine Methyl Ester Hydrochloride, 25 g, supplied in a sealed amber glass bottle with a polypropylene cap and safety label. |
| Container Loading (20′ FCL) | 20′ FCL: L-Lysine Methyl Ester Hydrochloride packed in sealed drums on pallets, securely loaded, ventilated, dry, avoiding contamination. |
| Shipping | L-Lysine Methyl Ester Hydrochloride is shipped as a fine chemical in sealed, moisture-resistant containers to preserve purity. Transport at ambient temperature, avoiding excessive heat and humidity. Handle with standard laboratory precautions; ensure compatibility with local regulations for non-hazardous amino acid derivatives. Store in a cool, dry, well-ventilated area upon receipt. |
| Storage | Store L-Lysine Methyl Ester Hydrochloride in a tightly sealed container in a cool, dry place, ideally at 2–8 °C or below. Protect from moisture, light, and air, as the material is hygroscopic and may degrade. Keep away from strong oxidizing agents and acids. Use under inert gas for long-term stability. |
| Shelf Life | Shelf life is 2 years if stored at -20°C, desiccated, and protected from moisture and light. |
In solution-phase peptide chain elongation where C-terminal L-lysine is temporarily masked as the methyl ester, L-lysine methyl ester hydrochloride is neutralized in anhydrous dimethylacetamide at 0–5°C with N-methylmorpholine at a 1.00–1.10 molar ratio to the hydrochloride; residual chloride above 0.1 wt% in the free base interferes with subsequent carbodiimide activation. The neutralized ester is coupled to an Nα-protected carboxyl component using EDC·HCl and HOBt at 1.0–1.2 equivalents relative to the limiting carboxyl group, while L-lysine methyl ester input is held at 0.95–1.05 molar equivalents to prevent excess free amine from capping activated ester intermediates. Saponification of the C-terminal ester, where required, is conducted with 1.0 M lithium hydroxide in tetrahydrofuran/water at a 3:1 v/v ratio and 0–5°C for 45–120 min; prolonged base contact isomerizes the α-carbon and reduces chiral purity below 99.0% as measured by USP <781> or equivalent chiral HPLC. Nα-protection is then performed with benzyl chloroformate at pH 8.5–9.5 and 20–25°C, using a 1.05–1.15 molar ratio of chloroformate to free amine. Incoming raw material used in active pharmaceutical ingredient intermediate production is controlled under ICH Q7 Section 7.1, with residual solvent testing according to USP <467> and Ph. Eur. 2.4.24, and residual chloride by ion chromatography. Terminal finished product types from this route include Nα-Boc/Nε-Z-L-lysine methyl ester, C-terminal lysine peptide fragments, peptidomimetic intermediates, and small-molecule peptide active pharmaceutical ingredients where the methyl ester protects the carboxylate during amide bond formation.
Schotten-Baumann acylation of L-lysine methyl ester hydrochloride with medium-chain fatty acid chlorides is conducted in a jacketed reactor at 0–5°C, using a solvent mixture of deionized water and acetone or dimethylacetamide at 60:40 v/v. The hydrochloride is dissolved at 10–20 wt%, and the pH is adjusted to 10.5–11.5 with 2.0–2.2 molar equivalents of aqueous sodium hydroxide; fatty acid chloride is then metered over 2.0–3.5 h at a 1.03–1.10 molar ratio to the lysine ester. Addition above 1.15 molar equivalents raises residual free fatty acid after saponification beyond 1.0%, while pH drift above 12.0 hydrolyzes the methyl ester to lysine carboxylate and generates off-spec anionic surfactant fractions. The batch is maintained under nitrogen, and the exotherm is controlled by chilled brine circulation to keep jacket outlet below 10°C. After acidification to pH 4.5–5.0, the precipitated Nε-acyl lysine methyl ester is washed with deionized water to chloride content below 0.5% and dried under vacuum at 40°C to moisture below 1.0%. Regulatory alignment for personal care terminal products references EC 1223/2009 for finished cosmetic formulations, REACH Annex VII for registration of the synthesized ester above 1 t/a, and OECD 301B ready biodegradability data generated on the acylated ester. Terminal finished product types include amino acid ester surfactant concentrates, rinse-off skin and hair cleansing bases, and powder-form amino acid-derived conditioning esters for compact shampoo formulations.
Conversion of L-lysine methyl ester hydrochloride to L-lysine methyl ester diisocyanate proceeds through neutralization of the hydrochloride with triethylamine at 1.00–1.05 molar equivalents in anhydrous chlorobenzene at 0–5°C, followed by filtration of triethylammonium chloride and phosgene addition at a 2.05–2.30 molar ratio of phosgene to free base. The α-amine and ε-amine are converted to isocyanate groups, while the methyl ester remains intact; residual water in the solvent must be below 0.01 wt% because water hydrolyzes phosgene to carbon dioxide and hydrogen chloride, reducing yield to below 75% and increasing pressure drop in the hydrogen chloride scrubber. The slurry is heated stepwise to 120°C over 4–6 h and held at 120°C for 2–3 h under a nitrogen sweep to remove dissolved hydrogen chloride; unconverted phosgene is consumed by a 10% sodium hydroxide scrubber. The crude product is vacuum-distilled at 95–110°C and 0.5–2.0 mbar, with isocyanate content verified by dibutylamine titration according to ISO 14896:2009. The finished L-lysine methyl ester diisocyanate is then reacted with polyether or polyester polyols at an NCO index of 1.05–1.20 in the presence of 0.01–0.05 wt% dibutyltin dilaurate; pot life in a 250 g batch at 25°C ranges from 20–45 min. Compliance for the downstream polyurethane product references ISO 11357-2:2020 for glass transition temperature, ASTM D412-16 for tensile properties, and REACH Annex VII for the diisocyanate monomer when placed on the EU market. Terminal finished product types include bio-based polyurethane adhesives, two-component coatings, and cast elastomers where the ester group of L-lysine methyl ester diisocyanate provides lower viscosity than aromatic isocyanates. Production-scale batches require dedicated phosgenation equipment because of acute inhalation toxicity and corrosive hydrogen chloride generation.
When Nε-methacryloyl-L-lysine methyl ester is prepared from L-lysine methyl ester hydrochloride, methacryloyl chloride is added at 0.80–0.90 molar equivalents to the free amine under Schotten-Baumann conditions at 0–5°C and pH 8.0–9.0; this substoichiometric ratio limits dicationic over-acylation at the α-amine and keeps free amine content high enough for post-polymerization conjugation. The resulting monomer is lyophilized and formulated in phosphate-buffered saline at 10–30 wt%, with poly(ethylene glycol) diacrylate crosslinker at 0.5–2.0 mol% and lithium phenyl-2,4,6-trimethylbenzoylphosphinate photoinitiator at 0.05–0.10 wt%. The precursor solution is filtered through a 0.22 μm polyethersulfone membrane and polymerized under 365 nm ultraviolet light at 3–8 mW cm⁻² for 2–10 min in a nitrogen-flushed mold; oxygen inhibition at the liquid-air interface reduces surface methacrylate conversion by more than 20% and is controlled with a 0.1 mm polyethylene terephthalate cover film. Cytocompatibility of the final hydrogel is evaluated according to ISO 10993-5:2009 using L929 cells, and sample preparation follows ISO 10993-12:2021; sterility testing references USP <71>. The pendant methyl ester and residual ε-amine allow subsequent peptide ligand coupling, while the methacrylate backbone provides dimensional stability for shaped implants. Terminal finished product types include photocured hydrogel films, cell encapsulation matrices, tissue-mimetic scaffolds, and drug-loaded hydrogel depots for sustained release. Published data for production-scale validation of this specific monomer in commercial medical device lines is limited; the formulation window is derived from laboratory-scale polymerization screening.
Covalent immobilization of L-lysine methyl ester onto epoxy-activated Sepharose 6B or polymethacrylate beads proceeds through primary amine attack on the oxirane ring at 25–30°C and pH 10.5–11.0, with the ligand dissolved at 5–20 μmol per mL of drained resin in 0.2 M sodium carbonate buffer. The methyl ester is retained as a chargeable carboxyl-protected arm, while the ε-amine selectively opens the epoxy ring; at pH above 11.5 ester hydrolysis generates free carboxylate that changes the ligand’s selectivity from cationic to zwitterionic and reduces batch-to-batch reproducibility. The reaction is agitated in a rotatory mixer at 20–30 rpm for 16–20 h, then the unreacted oxirane groups are blocked with 1.0 M ethanolamine at pH 8.0 for 4 h. The resin is washed with alternating 0.5 M sodium chloride in 0.1 M acetate buffer at pH 4.0 and 0.5 M sodium chloride in 0.1 M borate buffer at pH 8.5, and stored in 20% ethanol at 4–8°C. For process-scale downstream purification of biopharmaceuticals, the resin qualification references USP <665>, and manufacturing documentation for the ligand conjugation step follows ICH Q7 Section 5.4 for validation of affinity chromatography media preparation. Terminal finished product types include immobilized ligand affinity resins for enzyme purification, amino acid mimicry chromatography media, and analytical column packings for charge-based peptide separation. Published data for large-scale use of this specific ligand on production chromatography columns is limited; the ligand density range is based on small-scale resin screening and must be re-qualified per resin lot.
Competitive L-Lysine Methyl Ester Hydrochloride prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
L-Lysine methyl ester hydrochloride is the C-terminal methyl ester of L-lysine isolated as a hydrochloride salt. The product is commonly specified as H-Lys-OMe·HCl and is represented by the free-base formula C7H16N2O2 (160.21 g mol−1) and the monohydrochloride formula C7H17ClN2O2 (196.68 g mol−1). The dihydrochloride form, C7H18Cl2N2O2 (233.14 g mol−1), is frequently the commercial bulk entity indexed under CAS 26348-70-9. Because the carboxyl group is blocked as the methyl ester, the compound does not adopt the zwitterionic carboxylate structure of free L-lysine; the α- and ε-amino groups remain available for coupling after neutralisation. The substance is supplied as a white to off-white crystalline powder. Catalogue descriptors such as H-Lys-OMe·HCl and Lys-OMe·HCl are used interchangeably, but the term “hydrochloride” alone does not establish salt stoichiometry. The monohydrochloride and dihydrochloride differ in molecular weight, chloride content, and neutralisation requirements, and both forms may appear in supply chains under broadly similar descriptions.
Representative release criteria are summarised in the following matrix. These values reflect typical supplier certificates of analysis and should not replace a registered specification for a particular manufacturing route.
| Parameter | Test method | Typical acceptance range |
|---|---|---|
| Appearance | Visual inspection | White to off-white crystalline powder |
| Assay | HPLC area normalisation, Ph. Eur. 2.2.29 | ≥98.0% |
| Chloride stoichiometry | Argentometric titration or ion chromatography | 1.0–2.0 mol HCl per mol ester depending on salt form |
| Water content | Karl Fischer, USP <921> | ≤0.5% |
| Residue on ignition | USP <281> | ≤0.1% |
| Specific rotation | Polarimetry, c=1 in methanol, 20 °C | +14.0° to +16.0° for the dihydrochloride |
| Residual methanol | Headspace GC, ICH Q3C Class 2 | ≤3000 ppm |
The distinction between the monohydrochloride and dihydrochloride is critical for downstream neutralisation. A process addition of 1.0 mol equivalent of tertiary base per mol of substrate may be insufficient if the batch is actually the dihydrochloride, leaving residual protonated amine and reducing carbodiimide-mediated coupling efficiency. Conversely, use of the dihydrochloride molecular weight (233.14 g mol−1) for a monohydrochloride lot (196.68 g mol−1) alters molar loading calculations by approximately 18.5%. Specification sheets that report only HPLC area assay should therefore be supplemented with chloride titrimetry before pilot-plant batches are prepared.
The methyl ester hydrochloride differs from L-lysine monohydrochloride in solubility, charge state, and reactivity. L-Lysine monohydrochloride retains a free carboxylate and is readily soluble in water but only sparingly soluble in aprotic organic media. The methyl ester hydrochloride removes the carboxylate charge and dissolves in DMF, methanol, and dichloromethane at process-relevant concentrations. Nα-protected analogues such as Nα-Boc-L-lysine methyl ester hydrochloride provide selectivity at the ε-amine, whereas the unprotected methyl ester hydrochloride presents both α- and ε-amino groups after neutralisation. This dual availability is useful for symmetrical couplings but requires strict stoichiometric control when a single site is to be acylated.
| Parameter | L-Lysine Hydrochloride | L-Lysine Methyl Ester Hydrochloride | L-Lysine Methyl Ester Dihydrochloride |
|---|---|---|---|
| Molecular formula | C6H15ClN2O2 | C7H17ClN2O2 | C7H18Cl2N2O2 |
| Molecular weight | 182.65 g mol−1 | 196.68 g mol−1 | 233.14 g mol−1 |
| Carboxyl state | Free carboxylate | Methyl ester | Methyl ester |
| Chloride equivalents per mol | 1 | 1 | 2 |
| Solubility in DMF | Limited | High | High |
| Main synthetic role | Lysine source in aqueous and cell culture media | Carboxyl-protected lysine for peptide coupling and intermediates | Carboxyl-protected lysine; common commercial bulk form |
Solution-phase coupling with the methyl ester hydrochloride typically begins with dissolution in anhydrous DMF or dichloromethane at 0–5 °C. A tertiary amine such as N-methylmorpholine or N,N-diisopropylethylamine is added to liberate the amino groups; neutralisation is exothermic and batch temperature should be maintained below 10 °C in a jacketed vessel with mechanical stirring. Carbodiimide-mediated couplings using EDC·HCl or HATU are then conducted at 0–25 °C, with reaction progress followed by TLC or LC-MS. Because the α- and ε-amino groups are both available, the default outcome in the absence of a temporary side-chain protecting group is symmetrical bis-acylation. Site-selective acylation therefore requires either an Nα- or Nε-protected lysine derivative rather than the unprotected methyl ester hydrochloride. In scale-up, the neutralised free base is not isolated; it is generated in situ to avoid ester hydrolysis and carbamate formation upon exposure to atmospheric carbon dioxide.
The methyl ester is susceptible to base-catalysed hydrolysis. In process design, aqueous washes of the hydrochloride salt are typically maintained at pH 4–6; prolonged exposure to aqueous solutions above pH 8 can generate free L-lysine as the carboxyl-protecting group is cleaved. A practical operating envelope for workup is pH 4–6 and temperature 0–10 °C. At pH 9 and 25 °C, methyl ester cleavage can begin within the timescale of a normal wash cycle, although published kinetic parameters for this specific salt in mixed organic-aqueous systems are limited. The hydrochloride form is freely soluble in water and methanol, moderately soluble in ethanol, and poorly soluble in ethyl acetate and diethyl ether. Solvent compatibility is highest with polar aprotic solvents such as DMF and NMP; dichloromethane solutions of the free base are feasible but should be kept cold because the free amino groups can promote ester aminolysis on prolonged hold.
On manufacturing lines, moisture control is the main batch-to-batch variance. Because the powder is hygroscopic, open handling at relative humidity above 60% can raise water content by more than 0.5% within a single shift in a non-climate-controlled dispensing suite. Vacuum drying at 25–40 °C for 12–24 h reduces water content below 0.5% before anhydrous coupling, but drying above 50 °C should be avoided because discoloration and condensation impurities may increase. The material is incompatible with strong bases, which liberate the free amine and accelerate ester hydrolysis; acid chlorides and sulfonyl chlorides, which exothermically acylate the amino groups; and strong oxidising agents. The neutralised free base should be used immediately in the same reaction vessel and not stored.
The methyl ester is selected when a carboxyl-protecting group must be removed under mild alkaline hydrolysis rather than hydrogenolysis, because benzyl or tert-butyl esters require different cleavage conditions. Methyl ester cleavage is typically achieved with dilute sodium hydroxide or potassium carbonate in aqueous methanol at 0–20 °C, producing L-lysine and methanol. The methyl ester route is therefore used in sequences where a benzyl ether elsewhere in the molecule would be unstable under hydrogenation, or where the final product tolerance for residual palladium or toluene from deprotection is constrained. Compared with the ethyl ester, the methyl ester liberates methanol, which is easier to remove by vacuum stripping; compared with the tert-butyl ester, the methyl ester requires no strong acid deprotection and therefore avoids tert-butyl cation side reactions. However, the methyl ester has a smaller steric shield at the C-terminus, which can make the α-carbonyl more susceptible to racemisation under prolonged strong-base conditions.
Compared with L-lysine ethyl ester hydrochloride, the methyl ester has lower lipophilicity and a smaller ester alkyl group, which can increase coupling rate at the C-terminal carbonyl and simplify removal of the alcohol by-product. Compared with L-lysine benzyl ester hydrochloride, the methyl ester avoids hydrogenolytic deprotection and the associated palladium residues. Compared with L-lysine tert-butyl ester hydrochloride, the methyl ester avoids strong acid deprotection and isobutylene evolution in closed systems. The principal limitation is that methyl ester deprotection under aqueous alkali is less selective when other base-sensitive groups are present in the molecule.
Purification at pilot scale is usually not chromatographic. The hydrochloride is isolated by crystallisation from methanol/methyl tert-butyl ether or isopropanol. The main impurity classes are free L-lysine from ester hydrolysis, methyl lysine dimer from intermolecular aminolysis, and homologous esters from incomplete esterification. LC-MS with electrospray ionisation in positive mode is preferred for tracking these species because the hydrochloride salt gives poor long-term thermal stability in GC without derivatisation. Chiral purity should be confirmed by chiral HPLC or capillary electrophoresis when the product is used in an enantioselective route, because racemisation at the α-carbon is a known process risk under strong-base coupling conditions.
Regulatory documentation for L-lysine methyl ester hydrochloride is route-specific. The material is generally handled under amino acid derivative classification; no harmonised CLP Annex VI listing may exist for the single-hydrochloride form, so the supplier safety data sheet should be checked against CLP Regulation (EC) No 1272/2008. When used as a pharmaceutical intermediate, residual methanol is controlled to ≤3000 ppm under ICH Q3C Class 2, and elemental impurities are assessed under ICH Q3D. For custom synthesis, heavy metal specifications should default to the catalyst metals used in the final reduction or coupling steps; generic compendial limits alone are not sufficient for nitrosamine or mutagenic impurity control.
