SAFETY—Butyllithium Handling and Safety Practices

Routes to (2-chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]metha-none, 1, an intermediate in the manufacture of NK1-II inhibitor LY686017 are described which produce 1 in >75% yield and 95% purity. A highly selective telescoped ortho lithation/condensation/ oxidation process was developed and successfully scaled to the clinical pilot plant to produce 25 kg of 1. For the pilot-plant campaign, the lithiation step was developed to operate at -50 °C using commercial lithium diisopropylamide (LDA), and the oxidation step employed catalytic TEMPO as the primary and NaOCl as the terminal oxidant. After completion of the pilot-plant campaign second-generation approaches to 1 were developed to improve process greenness where the lithiation and condensation step were operated as warm as -10 °C, the highly efficient AZADO catalyst was used as a substitute for TEMPO in the Anelli-Montanari oxidation, and process mass intensity was reduced 25%.

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SAFETY—Butyllithium Handling and Safety Practices

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Alkylated sulfonated poly(arylene sulfone)s for proton exchange membranes

Alkylated sulfonated poly(arylene sulfone)s for proton exchange membranes

Process Development and Pilot-Plant Synthesis of (2-Chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone

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