This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
External Descriptors
Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.
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Application Protocols
Not applicable. No validated immunoassay or imaging protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For practical laboratory use, see:
Reaction & Applications: outlines typical derivatizations and uses in synthesis.
Reaction Conditions: provides general starting parameters for N-/O-functionalization and ester hydrolysis.
For solution preparation guidance, see Storage & Reconstitution.
Biological Roles
General biochemistry (literature): L-4-hydroxyproline is a post-translationally modified amino acid derived from L-proline via prolyl-4-hydroxylase. It is abundant in collagen, where the 4-hydroxyl group contributes to triple-helix stability through stereoelectronic effects and hydrogen bonding.
Relevance of the methyl ester hydrochloride form:
The methyl ester protects the carboxylate, enhancing membrane compatibility in synthetic settings and simplifying derivatization; the hydrochloride salt ensures the amine is protonated, improving aqueous solubility and handling.
In biological systems, esterases and aqueous conditions would revert esters toward the corresponding acids; however, this product is provided strictly for research/chemical synthesis and not for in vivo use.
Chiral pool utility (literature):
The L configuration at the α-carbon and defined stereochemistry at C-4 allow stereoselective construction of Hyp-containing peptides, peptidomimetics, and constrained analogs that mimic collagen motifs for biochemical studies.
Metabolic context (literature):
Hydroxyproline catabolism in organisms proceeds via oxidation to pyrroline derivatives and further to glyoxylate; these pathways are of interest in metabolism studies but are unrelated to the intended laboratory use of this methyl ester salt.
Note: No medical or clinical claims are made. This product is intended for research use only, as stated in the Product Data.
Buffer Applications
This compound is not a conventional buffering agent. As an amino acid ester hydrochloride, it lacks a free carboxylate and has a protonated amine, so it is not typically used to establish defined buffer ranges.
Practical note: Aqueous solutions of the HCl salt will be acidic due to the counterion; if used in biochemical assays, any apparent pH effect originates from added HCl rather than intrinsic buffering capacity. For buffering needs, select established buffers (e.g., phosphate, HEPES, MOPS) appropriate to your pH range.
For this item’s most relevant uses, see the Synthetic Utility and Reaction & Applications sections.
Green Alternatives
Green chemistry considerations for using L-4-hydroxyproline methyl ester hydrochloride center on solvent/auxiliary choices and protecting-group strategy, as the substrate itself is a chiral pool derivative from renewable biogenic sources (proline/hydroxyproline chemistry).
Solvent choices (literature, general):
Prefer ethanol or water/ethanol mixtures over methanol or chlorinated solvents for simple dissolutions and workups when compatible with the transformation.
Replace DCM with 2-MeTHF, EtOAc, or CPME for acylations/couplings; these offer lower toxicity and improved sustainability.
For peptide couplings, consider aqueous micellar catalysis (e.g., TPGS-750-M) or water-compatible coupling systems where possible.
Coupling reagents and additives:
Minimize use of benzotriazole-based additives (HOBt/HOAt) for safety; alternatives include OxymaPure or ethyl cyano(hydroxyimino)acetate (literature) with EDC or DIC.
Explore enzyme-mediated ester hydrolysis instead of strong base when converting the methyl ester to the acid, reducing energy and waste.
Protecting-group strategy:
Select temporary protections (e.g., carbonate or carbamate protections) that can be removed under mild, waste-minimizing conditions (e.g., catalytic hydrogenation for Cbz vs strong acids for Boc, depending on the substrate tolerance).
Tradeoffs:
Greener solvents may decrease solubility of the ionic salt; modest base neutralization to the free base followed by use of bio-based solvents (EtOAc, 2-MeTHF) can restore solubility but adds a processing step.
Water-rich systems increase risk of ester hydrolysis—plan accordingly (short residence times, lower temperature).
Pharmaceutical Uses
Role (general, non-clinical): a chiral building block for process and medicinal chemistry, enabling incorporation of L-4-hydroxyproline motifs into intermediates, peptidomimetics, and constrained scaffolds. The methyl ester protects the carboxyl group during upstream N- and O-functionalizations.
Formulation/excipient status: not a common excipient. No pharmacopeial monograph is referenced here. Any use in GMP manufacturing would require independent qualification and specification setting.
Handling benefits (literature):
Hydrochloride salt improves solid-state stability and aqueous solubility compared with the free base, easing weighing and solution preparation.
The esterified carboxyl simplifies crystallization of derivatives and can be hydrolyzed late-stage to unveil the acid when needed.
Typical operations in pharma R&D (literature):
Route scouting using this chiral pool derivative to set stereochemistry early.
Installation of amide/carbamate protections under mild conditions, followed by saponification to revert to the acid prior to coupling to other amino acids.
Note: No therapeutic or clinical claims are made. For regulated applications, consult internal quality systems and define acceptance criteria based on CoA and method validation.
Physical Properties
Item-specific properties from Product Data:
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Storage: Store at 2-8°C (per Product Data)
Shipping: Wet ice (per Product Data)
Literature/computed properties (reference only; not specifications):
Physical state: typically a crystalline hygroscopic solid for amino acid ester hydrochlorides
Molecular weight: ~181.6 g/mol (for C6H12ClNO3; literature calculation)
Solubility: generally high in water, methanol, ethanol; limited in nonpolar solvents (literature trends for amino acid ester HCl salts)
pKa: ammonium conjugate acid typically pKa ~9–10 for secondary amines in proline derivatives; as HCl salt the amine is fully protonated in neutral water (literature)
LogP: low; cationic salts are strongly hydrophilic (qualitative, literature)
Melting/decomposition: many amino acid ester HCl salts melt with decomposition; specific value not compiled (literature generalization)
Not provided in Product Data for this item (do not treat the following as specifications): boiling point, melting point, density, refractive index, water/peroxide/metal limits, UV cutoff.
Always consult the product CoA/SDS for item-specific, release-tested physical data.
Quality and Grades
Grade/purity (item-specific): Not specified for this item; refer to CoA/Spec Sheet for actual assay, residual solvents, and impurity profile.
Practical notes for this compound class:
Amino acid ester hydrochlorides are commonly supplied at high chemical purity for use as chiral building blocks. Relevant quality aspects include enantiomeric excess (ee), residual inorganic chloride balance, and limits on moisture since hydrolysis can generate the free acid.
For peptide and medicinal chemistry, specifications often include HPLC purity, optical rotation, and where applicable, chiral HPLC. If these are critical to your application, confirm on the CoA for this lot.
Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. Typically, such salts are shipped without stabilizers; low-temperature storage limits hydrolysis.
What the grade implies (general guidance):
“Research grade” materials are suited to discovery and process development but may not meet pharmacopeial monographs.
“HPLC grade” refers to solvents; for solids like this, look instead for “peptide,” “biochemical,” or “≥98%” indications on the specific CoA.
Fit-for-use checks:
Verify appearance and optical rotation on receipt if chirality is critical.
Perform a quick check by 1H NMR to ensure the ester remains intact (absence of carboxylate signals) and by chloride test if needed.
Reaction and Applications
As an L-proline-derived, 4-hydroxylated methyl ester in HCl salt form, this reagent serves as a versatile chiral building block.
Typical applications (literature):
Chiral pool synthesis: introduces the L-proline stereochemistry and a 4-hydroxy handle for downstream derivatization (e.g., etherification, acylation, oxidation to carbonyls).
N-functionalization: after base neutralization (e.g., DIPEA, TEA), the secondary amine undergoes acylation, sulfonylation, or carbamoylation to furnish protected derivatives (e.g., Boc-, Cbz-, or amide-bearing analogs).
O-functionalization: the C-4 alcohol can be acylated (Ac2O, acid chlorides/anhydrides) or converted via Mitsunobu-type reactions to invert configuration or to install other substituents (literature caution: secondary alcohol on a constrained ring may show substrate-specific reactivity).
Ester transformations: the methyl ester can be saponified to the acid (regenerating 4-hydroxy-L-proline hydrochloride or free base after pH adjustment) or engaged in aminolysis/transesterification under appropriate conditions.
Peptide/peptidomimetic synthesis: used to assemble Hyp-containing motifs; the methyl ester protects the C-terminus during N-side manipulations and is later hydrolyzed.
Practical tips:
Work under low moisture to limit premature ester hydrolysis.
When targeting selective N-acylation over O-acylation, use acylating agents at low temperature with hindered base and appropriate solvent (e.g., DMF) to bias toward the amine.
Monitor reactions by LC–MS/HPLC; the salt form often improves ionization and response.
Representative named methodologies: Steglich/EDC couplings (after saponification), Mitsunobu for O-substitution, and carbamate protections (Boc/Cbz) on the nitrogen (literature).
Reaction Conditions
General literature guidance for typical transformations of L-4-hydroxyproline methyl ester hydrochloride (actual conditions require optimization):
Liberation of free amine:
Dissolve the HCl salt in MeOH, EtOH, or DMF; add 1.1–2.0 equiv of a tertiary amine base (e.g., DIPEA, TEA). Stir 0–25°C for 10–30 min to form the free base in situ. Use immediately for acylation.
N-acylation/Carbamate formation:
Solvent: DMF, DCM, or 2-MeTHF. Base: DIPEA (2–3 equiv). Reagents: acyl chlorides/anhydrides or Boc2O/Cbz–Cl. Temperature: 0–25°C. Time: 0.5–4 h. Monitor for O-acylation; lowering temperature and using hindered bases favors N-acylation.
O-acylation (installing 4-O-acyl derivatives):
Solvent: pyridine, DMAP-catalyzed in DCM/DMF. Reagent: acyl chloride/anhydride (1.2–1.5 equiv). 0–25°C, 1–3 h. N-protection first (e.g., Boc) enhances O-selectivity.
Mitsunobu substitution at C-4 (for inversion or O-alkylation):
Solvent: THF or toluene. Reagents: DIAD/DEAD and PPh3 with the desired nucleophile (ROH, RCO2H). 0–25°C. Typical yields vary (40–80%); substrate-dependent.
Ester hydrolysis (saponification to acid):
Solvent: MeOH/H2O or THF/H2O (1:1). Base: NaOH or LiOH (1–2 equiv). 0–25°C, 0.5–2 h. Quench to pH ~2–3 to obtain the acid; isolate as free acid or adjust to desired salt.
Peptide coupling (after hydrolysis):
EDC·HCl/Oxyma or HATU/HBTU in DMF or NMP; base: DIPEA (2–3 equiv). 0–25°C, 0.5–4 h. Monitor by HPLC.
All parameters above are literature-style, general starting points and not item specifications. Confirm compatibility with your substrate and scale, and consult the SDS for safe handling.
Safety and Handling
GHS/Classification (item-specific): Not specified for this item; refer to the SDS for authoritative hazard classification, pictograms, and H-statements.
Likely hazards (general literature guidance for amino acid ester hydrochlorides):
Irritation: may cause skin, eye, and respiratory irritation; dust can be irritating.
Hygroscopic and acidic: HCl salts can be mildly acidic in aqueous solution; may cause discomfort on contact.
Special considerations for this compound class:
Acidic salt: solutions may have low pH; neutralize or dilute spills with appropriate absorbents. Avoid contact with bases that could liberate amine vapors; however, the parent amine is low volatility.
Moisture sensitivity: prolonged exposure to moisture can promote hydrolysis of the methyl ester to the acid; keep containers tightly closed.
Incompatibilities (general): strong bases (promote saponification), strong oxidizers (may oxidize the secondary alcohol), acylating agents (reactive toward the amine once deprotonated).
Recommended PPE: lab coat, safety glasses, appropriate chemical-resistant gloves (e.g., nitrile), and dust mask/respirator if handling powders that may become airborne. Use in a fume hood when weighing or preparing solutions.
First aid (overview; defer to SDS):
Inhalation: move to fresh air; seek medical attention if symptoms persist.
Skin/eyes: rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
Spill/Disposal: collect solids by gentle sweeping or HEPA vacuum; dispose in accordance with institutional and local regulations.
Solvent Selection
This item is a polar, ionic organic salt (amino acid ester HCl). Solvent choice should reflect its hydrophilicity and the desired reactivity of the amine and ester.
Miscibility/solubility (literature trends):
Water: typically freely soluble; generates acidic solutions due to HCl counterion.
Polar protic: methanol, ethanol, isopropanol—good solubility; useful for stock solutions and for ester hydrolysis studies.
Polar aprotic: DMF, DMSO—high solubility; excellent for acylation or coupling after in situ basification.
Nonpolar: poor solubility in ethers and hydrocarbons.
Choosing a medium:
For N-acylation: dissolve in MeOH/EtOH or DMF, then add an organic base (e.g., DIPEA) to liberate the free amine; alternatively, pre-neutralize in water and extract into an organic phase containing base.
For ester hydrolysis (saponification): aqueous MeOH/EtOH or THF/H2O systems facilitate controlled conversion to the acid.
For peptide coupling post-saponification: DMF, NMP, or mixed DMF/DCM are typical.
Small comparison (general):
Water vs MeOH: water maximizes salt solubility and control over pH; MeOH allows straightforward removal by evaporation but can participate in transesterification under acidic/basic conditions.
DMF vs DMSO: both dissolve salts well; DMF is easier to remove and more common in coupling workflows, whereas DMSO offers higher polarity but can complicate workup.
Drying: For strictly anhydrous operations, azeotropically co-evaporate with dry toluene or dry acetonitrile after neutralization to the free base (literature practice).
Storage and Reconstitution
Item-specific storage/shipping:
Store at 2-8°C (per Product Data). Keep container tightly closed in a dry place.
Shipped on wet ice (per Product Data). Allow to equilibrate to room temperature in a desiccated environment before opening to minimize moisture uptake.
Stability considerations (general):
Hygroscopic salts can absorb moisture; prolonged exposure promotes ester hydrolysis. Minimize headspace humidity; consider storing under inert gas for long-term stability.
Avoid repeated warming/cooling cycles. For multi-use, aliquot if preparing solutions.
Reconstitution/solution preparation:
Not specified for this item; refer to CoA/Spec Sheet for any lot-specific instructions.
Typical solvents (literature): water (forms acidic solutions), methanol, ethanol, and DMF/DMSO. For strictly anhydrous reactions, neutralize to the free base in situ with a tertiary amine and use dry aprotic solvent.
Typical stock concentrations (literature): 10–200 mg/mL, depending on solvent and application. Filter-sterilize aqueous stocks if needed for biochemical assays (0.22 µm PTFE/PES).
Shelf life: Not specified for this item; refer to CoA/Spec Sheet. Monitor by HPLC or 1H NMR over time for signs of ester hydrolysis (loss of –OCH3 signal) or formation of the free acid.
Research use only: As stated in Product Data, this product is for research use only.
Structure and Identity
L-4-Hydroxyproline methyl ester hydrochloride is a chiral amino-acid derivative (proline scaffold) bearing a secondary alcohol at C-4, the carboxyl group protected as a methyl ester, and present as the aminium chloride salt.
InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
SMILES: Not specified for this item; refer to CoA/Spec Sheet.
Computed/literature identity (for reference; not specification):
Core scaffold: pyrrolidine (proline ring)
Functional groups: secondary alcohol at C-4; methyl ester at C-1; protonated secondary amine (as HCl salt)
Stereochemistry: L-configuration at C-2 (α-carbon of amino acid); typical hydroxyproline stereochemistry at C-4 (trans-4-OH relative to the ring nitrogen) in the L isomer (literature)
Molecular formula (free salt): C6H12ClNO3 (literature calculation)
2D structure description (literature): a five-membered pyrrolidine ring with the ring nitrogen at position 1 (protonated in the HCl salt), the α-carbon (C-2) bearing the methyl esterified carboxyl substituent, and a hydroxyl substituent at C-4. The methyl ester is –COOCH3; chloride serves as the counterion.
Note: All structural constants not explicitly listed under Product Data are provided as general literature descriptors only; consult the product CoA for definitive identity data.
Synthetic Utility
Key functional features make this reagent highly versatile in synthesis (literature):
N–H (as ammonium in HCl salt): After neutralization, the secondary amine undergoes selective acylation, sulfonylation, and carbamoylation. Protecting-group strategies (Boc, Cbz, Fmoc) can be applied to direct subsequent O-chemistry.
4-OH handle: Enables acylation (esters, carbonates), etherification, or activation (e.g., mesylate/tosylate) for substitution or intramolecular cyclizations. Stereochemical outcomes are influenced by the rigid proline ring (neighboring group participation and conformational bias).
Methyl ester: Serves as a temporary C-terminus protection. It is compatible with many bases and nucleophiles at low temperature, yet can be hydrolyzed under controlled basic (NaOH, LiOH) or enzymatic conditions to regenerate the acid for peptide coupling.
Chiral pool advantage: The L- and trans-4-hydroxy stereochemistry provides pre-set chiral information for constructing polyfunctionalized pyrrolidines, peptidomimetics, and collagen-mimetic fragments.
Retrosynthetic value: Complex targets bearing a 4-substituted proline often disconnect back to this synthon. The orthogonality of N- and O-protection allows stepwise installation of side chains with minimized protecting-group clashes.
Analytical convenience: The salt form facilitates LC–MS (positive mode) and HPLC monitoring; methyl ester gives a characteristic singlet near 3.6–3.8 ppm in 1H NMR for –OCH3 (literature typical), aiding tracking of hydrolysis or derivatization.
Target Specificity
Not applicable. This product is a small-molecule amino acid derivative, not an antibody or affinity reagent. It does not have antigen/epitope specificity, clone information, isotype, or species reactivity. For intended uses, refer to the Synthetic Utility and Reaction & Applications sections.
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