Pilot Plant Preparation of an α_vβ₃ Integrin Antagonist. Part 1. Process Research and Development of a (S)-β-Amino Acid Ester Intermediate:  Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction

Abstract

Supporting InformationGeneral. Microanalyses were performed by Galbraith Laboratories or Atlantic Microlab. The actual charges of substrates and reagents are given below. The molar amounts are calculated based on the assays of the materials. Similarly, yields are calculated based on assay corrected moles of substrates and products. Proton ( 1 H) nuclear magnetic resonance (NMR) spectra were recorded on either a Unity Inova Varian 300 MHz or Unity Inova Varian 400 MHz spectrometer. 1 H NMR descriptions are reported as: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) or br (broad).Carbon ( 13 C) nuclear magnetic resonance (NMR) spectra were recorded on either a Unity Inova Varian 300 or Unity Inova Varian 400 spectrometer at 75 MHz and 100 MHz, respectively.Melting points were determined using a Laboratory Devises Mel-Temp Instrument equipped with a Fluke 51 Thermocouple. Thin-layer chromatography was performed on EM Science 0.25 nm Silica Gel 60, glass-backed plates with F 254 indicator. UV light was employed for visualization. Flash chromatography was performed on Universal Scientific 0-63 mesh Silica Gel. Liquid chromatography and mass spectrum analysis were performed on an Agilent 1100 Series LC/MSD model number G1946D equipped with an APCI ionization source and photodiiode array. Chiral HPLC method for separation of

A Catalyst‐free Addition Reaction of Zinc Amide Enolates to N‐Sulfonyl Imines

“…. In addition, application to a large scale production was also disclosed . Despite the remarkable expansion of the imino‐Reformatsky reaction, one interesting aspect is that, to the best of our knowledge, zinc enolates derived solely from α‐halo esters have been mainly used in the recent progress.…”

The role of pilot and demonstration plants in technological development: synthesis and directions for future research

“…These tools are often used in a trial-and-error-based approach in the sense that engineers carry out experiments in an iterative research process involving rules of thumb, expectations, and previous research (Clark et al 2004;Connolly, McGarry, and Sukhtankar 2005). Such experiments in PDPs are often complemented by research at the lab-scale level (Connolly, McGarry, and Sukhtankar 2005;Dyer et al 2002).…”

“…Another example is the study by Wieckert et al (2007, 195) concerning purity and mean particle size. Key results encompass both chemical and technical parameters in addition to process efficiency measures (see also Amutio et al 2012;Clark et al 2004;Nielsen, Li, and Rochelle 2013).…”

Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties

“…The asymmetric synthesis of β-amino ester derivatives or β-lactams has received much attention in organic synthesis over the past few years [3,14]. In 2011, Bull and coworkers reported the first example of an intramolecular cyclization of the ester enolate imine for the preparation of monocyclic β-lactams (Figure 2) [15].…”