Hydrochloric Acid → 4-[3,5-difluoro-4-(methylthio)-phenyl]-3-phenylfuran-2(5H)-one

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Reaction Steps

To a mixture of phenylacetic acid (4.2 g, 0.030 mol) and crude 2-bromo-1-[3,5-difluoro-4-(methylthio)-phenyl]ethanone (8.6 g, 0.030 mol) in anhydrous acetonitrile (100 mL) was added diisopropylethylamine (3.9 g, 0.030 mol). The reaction mixture was stirred for one hour at room temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (5.0 g, 0.032 mol) was added. After 2 hours the mixture was poured into dilute HCl and extracted with dichloromethane (1×200 mL, 2×75 mL). The combined extracts were dried using magnesium sulfate, and concentrated. The residue was treated with anhydrous acetonitrile (100 mL) and DBU (10.0 g, 0.065 mol), stirring at room temperature for 3 hours. The mixture was poured into dilute HCl and extracted with dichloromethane (1×200 mL, 2×50 mL). The combined extracts were dried using magnesium sulfate, and concentrated. Purification by silica gel chromatography using 5% dichloromethane/10% ethyl acetate in hexanes afforded 4-[3,5-difluoro-4-(methylthio)-phenyl]-3-phenylfuran-2(5H)-one as an orange liquid (7.2 g, 76%). 1H NMR (CDCl3/400 MHz) 7.37-7.41 (m, 5H), 6.97 (m, 2H), 5.09 (s, 2H), 2.48 (s, 3H). ESHRMS m/z 319.0601 (M+H+, Calcd 319.0604). Anal. Calcd for C17H12F2O2S: C, 64.14; H, 3.80. Found: C, 63.56; H, 3.54.

Provenance & Evidence