Diisobutylaluminum hydride → 1-ethyl-6-fluoro-3-(hydroxymethyl)-7,8-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one

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Reaction Steps

To a suspension of 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (40 g, 79 mmol) in Tetrahydrofuran (THF) (300 mL) was added TEA (12.08 mL, 87 mmol) and isobutyl chloroformate (11.39 mL, 87 mmol). The resulting mixture was stirred at r.t. for 1 h. LCMS showed completion of the reaction. Then the mixture was cooled down to −78° C. and a solution of DIBAL-H (158 mL, 236 mmol) in toluene (1.5 M) was added. The mixture was stirred at the same temperature for 1.5 h, LCMS indicated completion of the reaction. The reaction was quenched with sat. NH4Cl (aq.), warmed up to r.t., concentrated, diluted with sat. NH4Cl and extracted with dichloromethane twice. The organic mixture was filtered through Celite to remove any solids. The combined organic solution was then washed with brine and dried over sodium sulfate, filtered and the resulting filtrate was concentrated in vacuo to afford 1-ethyl-6-fluoro-3-(hydroxymethyl)-7,8-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one (33 g, 51.5 mmol, 65.3% yield) as yellow solid, which was used in the next oxidation step without further purification. LCMS: (M+H)+: 494.3.

Provenance & Evidence