Supplementary Material for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2007 Synthetic chemistry-led creation of a difluorinated biaryl ether non-nucleoside reverse transcriptase inhibitor Lyn H. Jones* Amy Randall, Oscar Barba and Matthew D. Selby Discovery Chemistry, Sandwich Laboratories, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ. Fax: +44 (0)1304 651821; Tel: +44 (0)1304 644256; E-mail: lyn.jones@pfizer.com General. Melting points were determined on a Gallenkamp melting point apparatus using glass capillary tubes and are uncorrected. Unless otherwise stated, all reactions were carried out under a nitrogen atmosphere, using commercially available anhydrous solvents. Thin-layer chromatography was performed on glass-backed pre- coated Merck silica gel (60 F254) plates, and FCC (flash column chromatography) was carried out using 40-63 μm silica gel. NMR spectra were carried out on a Varian Mercury 400, or Varian Inova 500 spectrometer in the solvents specified. Mass spectra were recorded on a Waters Micromass ZQ using atmospheric pressure chemical ionization (APCI). Combustion analyses were conducted by Exeter Analytical UK, Ltd, Uxbridge, Middlesex. Other abbreviations are used in conjunction with standard chemical practice. 2-[2-(3-Chloro-5-cyano-phenoxy)-phenoxy]-N-(2-methyl-6-sulfamoyl-pyridin-3- yl)-acetamide (1) O N H O N S NH 2 O O O Cl N Step A 3-Chloro-5-(2-methoxy-phenoxy)-benzonitrile (6)