Methanol → Methyl 2-hydroxy-2-(2-phenyl-1,3-thiazol-4-yl)acetate

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, trimethylsilylcyanide (824 μL, 6.6 mmol) was added at 0° C. to a solution of 2-phenyl-1,3-thiazole-4-carbaldehyde (1 g, 5.28 mmol) and zinc iodide (II) (166 mg, 0.52 mmol) in dichloromethane (30 mL). After 6 hours, the reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate and extracted with dichloromethane (2×20 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was used for the hydrolysis without further purification. Then, 2-(2-phenyl-1,3-thiazol-4-yl)-2-[(trimethylsilyl)oxy]acetonitrile was dissolved in anhydrous methanol (30 mL) and cooled at 0° C. and hydrogen chloride was bubbled for 2 minutes. The mixture was then warmed at room temperature for 20 h and concentrated under vacuum. A saturated solution of sodium bicarbonate (10 mL) was added to the residue and extracted with dichloromethane (2×15 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 70/30) to afford the desired alcohol (6a) as a white yellow oil (950 mg, 3.81 mmol, 72%).

Provenance & Evidence