Lithium diisopropylamide → 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-5-[(5-fluoro-pyridin-2-yl)-hydroxy-methyl]-3-methoxy-cyclopent-2-enone

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-cyclopent-2-enone (400 mg, 1.25 mmol) in anhydrous tetrahydrofuran (10 ml) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M in THF/heptanes/ethylbenzene; 0.76 m, 1.37 mmol) dropwise over a period of 5 minutes, and the reaction allowed to stir at 78° C. for 30 minutes. A solution of 5-fluoro-pyridine-2-carbaldehyde (171 mg, 1.37 mmol) in anhydrous tetrahydrofuran (1 ml) was then added dropwise over a period of 5 minutes before the reaction was allowed to warm to room temperature and stirred for a further 30 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (50 ml) and extracted with ethyl acetate (50 ml) and the organic later separated, dry loaded onto silica and purified by flash chromatography to give 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-5-[(5-fluoro-pyridin-2-yl)-hydroxy-methyl]-3-methoxy-cyclopent-2-enone (400 mg).

Provenance & Evidence