Sodium hydride → 2-Chloro-4-(4-chloro-2-fluoro-benzyloxy)-5-methoxy-benzaldehyde

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Reaction Steps

2-Chloro-4-hydroxy-5-methoxy-benzaldehyde (136, 0.548 g, 2.94 mmol, prepared as described in Example 46, Scheme 45, step 1) was dissolved in N,N-dimethylformamide (40 mL) and sodium hydride (60% dispersion in mineral oil, 0.200 g, 5.00 mmol) was added. After 20 minutes, 1-bromomethyl-4-chloro-2-fluoro-benzene (139, 685 μL, 5.00 mmol) was added to the reaction mixture. The reaction was stirred at room temperature under an atmosphere of nitrogen for 5.5 hours. The reaction was concentrated to dryness in vacuo. The reaction was resuspended in water/saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography, eluting with 5-35% ethyl acetate in hexane give a white solid (140, 0.942 g, 97%), consistent with the desired compound by 1H-NMR.

Provenance & Evidence