Imidazole → Ethyl 4-(tert-butyldimethylsilyloxy)-3-methoxybenzoate

Participants

Reaction Steps

Tert-butyldimethylsilyl chloride (12 g) was added to a mixture of ethyl vanillate (15 g), imidazole (13 g) and tetrahydrofuran (100 ml) and the mixture was stirred at ambient temperature for 48 hours. The mixture was filtered and evaporated to give ethyl 4-(tert-butyldimethylsilyloxy)-3-methoxybenzoate (25.1 g). A solution of the product so obtained in tetrahydrofuran (50 ml) was cooled to -70° C. and to this was added a cooled (-70° C.) solution of thiazol-2-yl-lithium [prepared by adding 2-bromothiazole (14.1 g) to a mixture of n-butyl-lithium (1.5M in hexane, 57.3 ml) and diethyl ether (30 ml) which had been cooled to -70° C⟧ The mixture was stirred for 16 hours and allowed to warm to ambient temperature. The mixture was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate (3×100 ml). The combined extracts were washed with water and with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column chromatography using increasingly polar mixtures of methylene chloride and ethyl acetate as eluent. There was thus obtained 4-hydroxy-3-methoxyphenyl 2-thiazolyl ketone (4.5 g) in 24% yield, m.p. 103° C.

Provenance & Evidence