Hydrochloric Acid → (5-(Benzyloxy)-2-methoxyphenyl)(5-methylthiazol-2-yl)methanone

Participants

Reaction Conditions

Reaction Steps

To a stirring mixture of 5-methylthiazole (3.80 g, 38.2 mmol) in dry THF (200 mL) was added n-BuLi (2.5 M in hexane, 15.3 mL, 38.2 mmol) drop wise over 20 minutes at −78° C. under nitrogen atmosphere. The mixture was stirred between −78° C. and −60° C. for 1.5 h and then cooled to −78° C. A solution of methyl 5-(benzyloxy)-2-methoxybenzoate (10.4 g, 38.2 mmol) in THF (50 mL) was added drop wise over 30 minutes. The resulting mixture was stirred at −78° C. for 30 minutes and warmed to room temperature with stirring overnight. The mixture was cooled to 0° C. and treated with water (50 mL). The resulting mixture was adjusted to pH around 6 with HCl (1N). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc (3:1) to afford (5-(benzyloxy)-2-methoxyphenyl)(5-methylthiazol-2-yl)methanone (2.5 g, 19%) as a yellow gel. 3.0 g of starting material methyl 5-(benzyloxy)-2-methoxybenzoate was recovered.

Provenance & Evidence