Acetaldehyde → 1-{5-[5-(4-Isopropoxyphenoxy)-1,3,4-thiadiazol-2-yl]thien-2-yl}ethanol

Participants

Reaction Conditions

Reaction Steps

A solution of Example 24D (0.35 g, 1.1 mmol) in tetrahydrofuran (14 mL) was cooled to −78° C. under a nitrogen atmosphere and was treated with n-butyllithium (2.5M in hexanes, 0.925 mL, 2.31 mmol) drop wise over 5 minutes. After stirring at −78° C. for 10 min, acetaldehyde (0.309 mL, 5.5 mmol) was added and the reaction was allowed to warm to −30° C. The reaction was stirred for 10 min at −30° C. and 1N HCl (20 mL) was added. The resulting bilayer was stirred at 25° C. for 5 min and was extracted with ethyl ether (80 mL). The organic phase was washed with brine (20 mL), dried (Na2SO4), filtered, and evaporated to provide 0.74 g of a light brown oil. The residue was purified by flash chromatography on silica gel eluting with a solvent gradient from 10% to 35% ethyl acetate in hexanes to provide 0.34 g (86%) of the title compound as a pale green oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.48 (d, J=3.68 Hz, 1H) 7.39 (d, J=9.19 Hz, 2H) 7.02 (d, J=9.19 Hz, 2H) 6.96 (dd, J=3.68, 0.74 Hz, 1H) 5.78 (d, J=5.15 Hz, 1H) 4.88-5.06 (m, 1H) 4.63 (heptet, J=5.88 Hz, 1H) 1.43 (d, J=6.25 Hz, 3H) 1.28 (d, J=5.88 Hz, 6H); MS (ESI) m/z 363 (M+H)+.

Provenance & Evidence