Publications by authors named "Matthew H Yates"

Flow chemistry was initially used for speed to early phase material delivery in the development laboratories, scaling up chemical transformations that we would not or could not scale up batch for safety reasons. Some early examples included a Newman Kwart Rearrangement, Claisen rearrangement, hydroformylation, and thermal imidazole cyclization. Next, flow chemistry was used to enable safe scale up of hazardous chemistries to manufacturing plants.

View Article and Find Full Text PDF
Article Synopsis
  • The aza-Henry reaction can be risky when scaling up due to hazards from peracids and nitroalkanes, leading to the need for safer alternatives.
  • A new continuous and scalable platform was developed to create aliphatic nitroalkanes by oxidizing oximes using peracetic acid, which allows direct use of the nitroalkane in the aza-Henry reaction.
  • The innovative pipe-in-series reactor improves safety and efficiency, enabling the production of purified nitroalkane solutions for enantioselective reactions while avoiding dangerous intermediate isolation.
View Article and Find Full Text PDF

Control and optimization of the physical properties of a drug substance (DS) are critical to the development of robust drug product manufacturing processes and performance. A lack of isolatable, for example, crystalline, DS solid forms can present challenges to achieving this control. In this study, an isolation scheme for an amorphous DS was developed and integrated into the synthetic route producing DS with optimized properties.

View Article and Find Full Text PDF

A stereoselective aza-Henry reaction between an arylnitromethane and Boc-protected aryl aldimine using a homogeneous Brønsted acid-base catalyst was translated from batch format to an automated intermittent-flow process. This work demonstrates the advantages of a novel intermittent-flow setup with product crystallization and slow reagent addition which is not amenable to the standard continuous equipment: plug flow tube reactor (PFR) or continuous stirred tank reactor (CSTR). A significant benefit of this strategy was the integration of an organocatalytic enantioselective reaction with straightforward product separation, including recycle of the catalyst, resulting in increased intensity of the process by maintaining high catalyst concentration in the reactor.

View Article and Find Full Text PDF

The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has advanced significantly over the past decade, and these reactions have potential to address important green-chemistry challenges in the pharmaceutical industry. This potential has been unrealized, however, because safety concerns and process constraints hinder large-scale applications of this chemistry. These limitations are addressed by the development of a continuous-flow tube reactor, which has been demonstrated on several scales in the aerobic oxidation of alcohols.

View Article and Find Full Text PDF