Cesium carbonate → Thiazyl chloride

Participants

Reaction Steps

Thiazyl chloride 4.8 was prepared according to the method described in Example 2 starting from commercially available 4-methyl-2-(4-methylphenyl)-1,3-thiazole-5-carboxylic acid. The phenol 3.5 (276 mg, 1.10 mmol) was dissolved in 5 mL of DMF and thiazyl chloride 4.8 (317 mg, 1.16 mmol) was added followed by cesium carbonate (715 mg, 2.20 mmol). The reaction was stirred for 14 hours and diluted with 250 mL of EtOAc. The organic layer was washed with 1N HCl (aq) (50 mL), saturated NaHCO3 (aq) (50 mL), and brine (2×50 mL). The organic layer was dried with MgSO4, filtered, and concentrated under reduced pressure. The residue was dissolved in 15 mL THF and 0.111 N NaOH (aq) (15 mL, 1.65 mmol) was added. MeOH (10 mL) was added and the mixture became homogeneous. The solution was stirred for 8 hours and concentrated to remove the organic solvent. The slurry was diluted with water (50 mL) and DCM (300 mL). The mixture was adjusted with 2N HCl (aq) to a pH of 2. The material was extracted with DCM (3×75 mL). The organic layer was dried with Na2SO4 and concentrated under reduced pressure. The residue was flashed through silica with 5% MeOH in DCM to afford dimethylamide 4 (346 mg, 0.79 mmol) as a white solid. 1H NMR (400 MHz) (CDCl3) δ 7.83 (d, J=8.0, 2H); 7.20-7.28 (m, 4H); 6.96 (d, J=8.5, 2H); 5.17 (s, 2H); 4.22 (dd, J=3.8, 8.9 Hz, 1H); 3.13 (dd, J=8.9, 15.8 Hz, 1H); 3.02 (s, 3H); 2.93 (s, 3H); 2.80 (dd, J=3.8, 15.8 Hz, 1H); 2.51 (s, 3H); 2.41 (s, 3H).

Provenance & Evidence