N-[(1R)-2-[1,1'-Biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid 1,1-dimethylethyl ester
[CAS 1426129-50-1]

Identification

• Classification: API >> Circulatory system medication >> Angiotensin converting enzyme and receptor inhibitor
• Name: N-[(1R)-2-[1,1'-Biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid 1,1-dimethylethyl ester
• Synonyms: tert-butyl N-[(2R)-1-hydroxy-3-(4-phenylphenyl)propan-2-yl]carbamate
• Molecular Formula: C₂₀H₂₅NO₃
• Molecular Weight: 327.42
• Protein Sequence: X
• CAS Registry Number: 1426129-50-1
• EC Number: 810-281-9
• SMILES: CC(C)(C)OC(=O)N[C@H](CC1=CC=C(C=C1)C2=CC=CC=C2)CO

Properties

• Solubility: Practically insoluble (0.046 g/L) (25 °C), Calc.^*
• Density: 1.103±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 496.8±55.0 °C 760 mmHg (Calc.)^*
• Flash point: 254.3±31.5 °C (Calc.)^*
• Index of refraction: 1.538 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302
• Safety Statements: P280-P305+P351+P338

chemBlink Chemical Story

N-[(1R)-2-[1,1′-biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamic acid 1,1-dimethylethyl ester is a stereochemically defined biphenyl-containing carbamate derivative featuring a protected amine functionality, a hydroxymethyl-substituted chiral ethyl linker, and a bulky tert-butyl ester protecting group. The structure is characterized by a combination of aromatic rigidity and aliphatic flexibility, resulting in a molecule with distinct hydrophobic and polar regions.

The core aromatic component is the [1,1′-biphenyl]-4-yl group. Biphenyl consists of two benzene rings connected by a single carbon–carbon bond. This linkage allows partial rotational freedom, although steric repulsion between ortho hydrogen atoms typically results in a non-coplanar arrangement of the rings. The biphenyl moiety contributes significant hydrophobic character and provides an extended π-electron system capable of aromatic stacking interactions.

Attached to the biphenyl group is a chiral ethyl linker bearing two substituents: a hydroxymethyl group and a carbamate-protected amine. The (1R) configuration defines the absolute stereochemistry of this carbon center, fixing the spatial orientation of the substituents and influencing the overall three-dimensional conformation of the molecule.

The hydroxymethyl group (–CH₂OH) introduces a polar functional site capable of hydrogen bonding. The oxygen atom serves as both hydrogen-bond donor (via the hydroxyl hydrogen) and acceptor (via lone pairs), contributing to localized hydrophilicity within an otherwise largely hydrophobic framework.

The carbamate functionality is present in the form of a tert-butyl carbamate (Boc) protecting group. Carbamates consist of an amide-like linkage where a carbonyl group is bonded to both nitrogen and oxygen atoms. In this structure, the nitrogen is substituted by the chiral carbon chain, while the oxygen is attached to a tert-butyl group through an ester linkage. Resonance between the carbonyl and nitrogen imparts partial double-bond character to the N–C bond, reducing nitrogen basicity and restricting rotation.

The tert-butyl group is a bulky, highly hydrophobic substituent composed of a central carbon attached to three methyl groups. This steric bulk plays an important role in shielding the carbamate functionality and influencing both solubility and conformational accessibility.

From a structural perspective, the molecule contains both rigid and flexible elements. The biphenyl group is relatively rigid due to aromaticity, while the ethyl linker provides flexibility around single bonds. The carbamate group introduces additional conformational restriction due to resonance stabilization.

Physicochemically, the molecule is amphiphilic. The biphenyl moiety contributes strong hydrophobic character, while the hydroxymethyl group and carbamate carbonyl introduce polar and hydrogen-bonding capabilities. This dual character influences intermolecular interactions, including hydrogen bonding in polar environments and π–π interactions in nonpolar environments.

Chemically, the hydroxymethyl group can undergo oxidation to form aldehyde or carboxylic acid derivatives under appropriate conditions. The carbamate (Boc) group is generally stable under neutral and basic conditions but can be cleaved under acidic conditions to reveal the corresponding amine. The biphenyl aromatic system is chemically stable under most standard conditions but may participate in electrophilic substitution under strong activating conditions.

The stereochemical center plays an important role in defining the molecule’s three-dimensional structure and may influence how functional groups are oriented relative to each other, particularly the spatial relationship between the biphenyl group and the carbamate-protected amino functionality.

Without specific literature confirming biological or functional applications for this exact compound, no claims can be made regarding its use. Based on structural analysis alone, it is best described as a chiral biphenyl-substituted amino alcohol derivative bearing a tert-butyl carbamate protecting group, combining aromatic rigidity, hydrogen-bonding capability, and a protected amine within a single multifunctional molecular framework.

References

2019. Pd(NHC)(cinnamyl)Cl-catalyzed Suzuki cross-coupling reaction of aryl sulfonates with arylboronic acids. Molecular Diversity.
DOI: 10.1007/s11030-019-10001-4

2016. Sacubitril. Pharmaceutical Substances