p-Toluenesulfonic acid → (2z)-2-(3-Butyl-1,3-thiazol-2(3h)-ylidene)-1-(5-chloro-2-methoxyphenyl)ethanone

Participants

Reaction Steps

To a stirred suspension of NaH (60% in mineral oil, 0.04 g, 1 mmol) in anhydrous DMF (3 mL) at 0° C. was added 5-chloro-2-methoxyacetophenone (0.15 g, 1 mmol) followed by subsequent addition of n-butylisothiocyanate (0.24 mL, 2 mmol) in DMF (3 mL). The mixture was stirred at 0° C. for 2 hours after which 2-bromo-1,1-dimethoxyethane was added. The reaction mixture was stirred for 2 hr and then poured into brine, extracted with EtOAc. The organic layer was washed with brine (3×30 mL), dried (MgSO4) and concentrated. The residue was dissolved in toluene (10 mL) then treated with p-toluenesulfonic acid (1.5 mmol) and refluxed for 6 hr. The reaction mixture was concentrated and partitioned between EtOAc and saturated NaHCO3. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography eluting with 50% ethyl acetate in hexane to provide the title compound as a yellow solid. (10 mg). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.93 (t, J=7.3 Hz, 3 H), 1.32 (dd, J=15.1, 7.3 Hz, 2 H), 1.72 (t, J=7.3 Hz, 2 H), 3.86 (s, 3 H), 4.01 (t, J=7.1 Hz, 2 H), 6.57 (s, 1 H), 6.81 (d, J=4.4 Hz, 1 H), 7.12 (d, J=8.8 Hz, 1 H), 7.33-7.48 (m, 1 H), 7.34-7.49 (m, 1 H), 7.65 (d, J=3.1 Hz, 1 H). MS (DCI), m/z 324 (M+H)+.

Provenance & Evidence