Thioguaiacol → (R)-N-[2-Chloro-4-(2-methoxyphenylthio)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

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Reaction Steps

Tetrakis(triphenylphosphine)palladium(0) (0.03 g) was added to a deoxygenated mixture of (R)-N-[2-chloro-4-iodophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Method 20) (0.2 g), 2-methoxybenzenethiol (0.064 ml) and sodium methoxide (0.058 g) in ethanol (10 ml). The mixture was further deoxygenated by evacuation and refilling with argon (3 cycles) then heated under reflux with stirring under argon for 18 hours, treated with a further portion of tetrakis(triphenylphosphine)palladium(0) (0.03 g), heated a further 24 hours then cooled and filtered. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 0-10% ethyl acetate/hexane to give the title compound (0.166 g) as an oil. NMR (CDCl3): 1.75 (s, 3H), 3.7 (br s, 1H), 3.85 (s, 3H), 6.9 (m, 2H), 7.2 (m, 1H), 7.3 (dd, 1H), 7.35 (m, 2H), 8.3 (d, 1H), 9.8 (br s, 1H); MS: 404 (M−H)−.

Provenance & Evidence