Asymmetric Synthesis of Netarsudil: A New Therapeutic for Open-Angle Glaucoma was written by deLong, Mitchell A.;Sturdivant, Jill M.. And the article was included in Synthesis in 2019.Name: Methyl 2-(4-(hydroxymethyl)phenyl)acetate This article mentions the following:
The asym. synthesis of a Rho kinase/norepinephrine transport inhibitor, netarsudil, the active component in the recently FDA-approved product Rhopressa, is described herein. This concise six-step synthetic route utilizes the 2,4-dimethylbenzoate ester of a phenylacetic acid as the backbone of the β-amino acid’s framework. A chiral enolate of the Evans auxiliary, ( R)-4-benzyloxazolidin-2-one, is used to direct the formation of the ( S)-stereocenter by incorporating the N-Boc-protected β-amino Me arm with high diastereoselectivity (96:4 dr) using N-Boc-1-(aminomethyl)benzotriazole as the electrophile. Uniquely, 2,2,2-trichloro-1,1-dimethylethyl chloroformate is used as a non-racemizing activating agent for the coupling reaction between the chiral (S)-3-[(tert-Butoxycarbonyl)amino]-2-(4-{[(2,4-dimethylbenzoyl)oxy]methyl}phenyl)propanoic acid and 6-aminoisoquinoline to provide N-Boc-protected netarsudil in good yield and excellent enantiomeric purity (63%, 98% ee). Final acidic deprotection and recrystallization provides netarsudil (>99% ee), an ophthalmic agent used for the treatment of patients with open-angle glaucoma. In the experiment, the researchers used many compounds, for example, Methyl 2-(4-(hydroxymethyl)phenyl)acetate (cas: 155380-11-3Name: Methyl 2-(4-(hydroxymethyl)phenyl)acetate).
Methyl 2-(4-(hydroxymethyl)phenyl)acetate (cas: 155380-11-3) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Name: Methyl 2-(4-(hydroxymethyl)phenyl)acetate
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Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics