Diisopropylamine → 4,4,4-Trifluoro-3-hydroxy-3-methyl-1-[4-(pyrid-4-ylsulfonyl)phenyl]but-1-yne

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (0.37 mL, 2.66 mmol) in tetrahydrofuran (11 mL) at -20° C. was added n-butyllithium (0.9 mL of 2.5M solution in hexanes, 2.25 mmol) and the resulting solution was stirred for 25 minutes at -20° C. before being cooled to -78° C. To this was added a solution of 4-(4-pyridylsulfonyl)phenylacetylene (0.5 g, 2.05 mmol) in tetrahydrofuran (3 mL) over a five minute period. The mixture was stirred for an additional 15 minutes at -78° C. To this was added 1,1,1-trifluoroacetone (0.20 mL, 2.25 mmol) in one portion. After stirring the mixture at -78° C. for 20 minutes, it was quenched with water, warmed to ambient temperature and the pH adjusted to 7.0 with saturated aqueous NH4Cl . The solution was evaporated and the resulting residue was partitioned between water and ethyl acetate. The ethyl acetate layer was separated, washed (brine), dried and evaporated. The resulting brown oil was purified by chromatography, with ethyl acetate:dichloromethane as the eluent (1:5), to give the title compound as a white solid (0.36 g, 50%); mp 122°-125° C.; NMR (CDCl3): 1.73 (s,3, CH3), 3.37 (s,1, OH), 7.61 (d,2, J=8.2, At), 7.76 (d,2, J=5.1, Ar), 7.93 (d,2, J=4); MS: m/z=356(M+ 1). Analysis for C16H12F3NO3S: Calculated: C, 54.08; H, 3.40; N, 3.94; Found: C, 53.99; H, 3.41; N, 3.75.

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