Citric Acid → (6-Hydroxy-3,4-dihydro-1H-isoquinolin-2-yl)-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanone

Participants

Reaction Steps

4-Methyl-2-[4-(trifluoromethyl)phenyl]-5-thiazolecarboxylic acid (450 mg, 1.6 mmol), 1-hydroxybenzotriazole (260 mg, 1.9 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (370 mg, 1.9 mmol) were added to 6-hydroxy-1,2,3,4-tetrahydroisoquinoline hydrobromide (300 mg, 1.3 mmol) in 2 ml of triethylamine and 6 ml of methylene chloride. The reaction was stirred under N2 at RT for 18 hrs. The reaction was diluted with 100 ml CH2Cl2 and made acidic with 10% citric acid. The organic layer was separated and the aqueous phase was extracted with 2×100 ml CH2Cl2. The organic phases were combined, washed with H2O, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (40% EtOAc/Hexanes) to yield 229 mg (42%) of the title product of this preparation as a white solid.

Provenance & Evidence