2-(3-chlorophenoxy)ethanethioamide

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-(4-fluorophenyl)-2-(4-methylthiophenyl)-2-bromo-ethanone (1.98 g, 5.84 mmol) (Example 1, Step 3) and 3-chlorophenoxy thioacetamide (1.18 g, 5.85 mmol) in 15 mL of acetonitrile and 10 mL of ethanol was heated to reflux for 16 hours. The solution was diluted with methanol, cooled to 0° C. in an ice bath and a precipitate formed that was removed by filtration. The solid was air dried and then recrystallized from methanol to provide (1.67 g; 65%),of pure 2-((3-chlorophenoxy)methyl)-4-(4-fluorophenyl)-5-(4-methylthiophenyl)thiazole: mp 106°-110° C., 1NMR (CDCl3) 300 MHz 7.50 (m, 2H), 7.30-7.15 (m, 5H), 7.09-6.87 (m, 5H), 5.38 (s, 2H), 2.50 (s, 3H). 19F NMR (CDCl3) -113.58 (m). Mass spectrum M+ =441. to reflux for 16 hours a precipitate formed that was removed by filtration dried recrystallized from methanol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-(2-fluorophenyl)-2-(4-methylthiophenyl)-2-bromo ethanone, (1.64 g, 4.8 mmol) (Example 34, Step 3) and 3-chlorophenoxy thioacetamide (0.98 g, 4.8 mmol) in 25 mL of acetonitrile was heated to reflux for 14 hours. The solution was diluted with methanol, cooled to 0° C. in an ice bath and a precipitate formed that was removed by filtration to provide pure 2-((3-chlorophenoxy)methyl)-4-(2-fluorophenyl)-5-(4-methylthiophenyl)thiazole (0.69 g; 32%). The filtrate was concentrated in vacuo, and the residue dissolved in ethyl acetate, washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to provide additional product that was crystallized from a mixture of dichloromethane and isooctane to provide 200 mg of additional material for a total yield of 890 mg (42%): mp 115°-118° C.: 1H NMR (CDCl3) 300 MHz 7.52-6.90 (m, 12H), 5.38 (s, 2H), 2.46 (s, 3H). 19F NMR (CDCl3) -113.61 (m). High resolution mass spectrum calc'd. for C23H17ClFNOS2 (M+): 441.0424. Found: 441.0467. to reflux for 14 hours a precipitate formed that was removed by filtration