Hydrochloric Acid → Ethyl 2-[(3-fluoro-2-hydroxy-4-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)hydrazono]propanoate

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Reaction Steps

To an ice-cooled and stirred mixture of 6-amino-2-fluoro-3-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenol (4.2 g) and concentrated hydrochloric acid (2.6 mL) in ethanol (40 mL) and water (10 mL) was added portionwise a solution of sodium nitrite (1.16 g) in water (20 mL) at −10° C. After stirred at −10° C. for 10 min, the solution was added dropwise to a cooled solution of potassium hydroxide (85%, 2.8 g) and ethyl 2-methyl-3-oxobutanoate (2.2 mL) in ethanol (25 mL) and water (25 mL) below −5° C. After stirred at −5 to −10° C. for 30 min, the mixture was partitioned between ethyl acetate and aqueous citric acid solution. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residual brown oil was purified by silica gel chromatography (ethyl acetate:hexane=2:1 to 4:1, volume ratio) to give the title compound (4.94 g, 85%) as light brown prisms. MS 412 (MH+).

Provenance & Evidence