Jacqueline E. Milne

An efficient and scalable Ritter reaction for the synthesis of tert-butyl amides.

A scalable procedure for the conversion of nitriles to N-tert-butyl amides via the Ritter reaction was optimized employing tert-butyl acetate and acetic acid. The reaction has a broad scope for aromatic, alkyl, and alpha,beta-unsaturated nitriles.

Iodide-Catalyzed Reductions: Development of a Synthesis of Phenylacetic Acids

A new convenient and scalable synthesis of phenylacetic acids has been developed via the iodide catalyzed reduction of mandelic acids. The procedure relies on in situ generation of hydroiodic acid from catalytic sodium iodide, employing phosphorus acid as the stoichiometric reductant.

Pd-Catalyzed Deoxygenation of Mandelate Esters

A new approach to the synthesis of phenylacetic acids and esters has been developed via the palladium-catalyzed deoxygenation of mandelate esters.

An Efficient and Scalable Ritter Reaction for the Synthesis of t‐Butyl Amides

Methyl 4-cyanobenzoate Acetic acid Tert-Butyl acetate Sulfuric acid Ammonium acetate Methyl 4-(tert-butylcarbamoyl)benzoate Keywords: Ritter reaction; Butyl amides; Substrate scope; Sulfuric acid; Scalable method; Acetic acid; Safety; Waste disposal

Application of two‐dimensional selective‐TOCSY HMBC for structure elucidation of impurities in mixture without separation

In the pharmaceutical industry, regulatory expectations driven by patient safety considerations make structure elucidation of impurities at levels greater than 0.1% in the active pharmaceutical ingredient (API) of primary interest. Impurities can be generated from isomers in starting materials, or produced from different process steps toward the final API. Proton peaks belonging to different impurities could be potentially identified in the one‐dimensional 1H NMR spectrum, when evaluated in combination with two‐dimensional (2‐D) COSY and HSQC data. However, in 2‐D HMBC data, correlation responses from different impurities may overlap with those from the major component, causing uncertainty of long‐range proton to carbon correlations and quaternary carbon assignments. This observation prompts us to design the 2‐D selective‐TOCSY HMBC experiment to distinguish responses from different impurities in mixtures to obtain 2‐D NMR data for each impurity, thus eliminating the use of a chromatographic isolation step to obtain material for NMR analysis. This methodology is demonstrated for structure elucidation of impurities ranging from 8.2% in the raw material to 0.4% in the API in this study, and would be particularly useful for industrial samples in which the solubility and availability of material are not an issue. Copyright