Imidazole → 3-Fluoro-4-triisopropylsilanyloxybenzaldehyde

Participants

Reaction Steps

Add triisopropylsilyl chloride (74.32 g, 0.3855 mol), followed by DMF (25 mL), to a solution of 3-fluoro-4-hydroxybenzaldehyde (45.01 g, 0.3213 mol) and imidazole (43.74 g, 0.6425 mole) in DMF (313 mL) at 25-29° C. in a steady stream over 2 min. Stir for 1 hr at room temperature till the reaction complete as determined by HPLC (Column: 4.6 mm×25 cm Zorbax RX-C8; eluant: 50/50 0.1% TFA:acetonitrile, flow rate 2 mL/min; detector: 230 nm; temperature: 22° C.; injection: 10 μL). Pour the reaction mixture into saturated aqueous ammonium chloride solution (1 L) and extract with ether (3×1 L). Combine the ether layers, wash with brine (2×750 mL) and dried over sodium sulfate. Filter and concentrate to give a yellow oil (106.3 g). Purify the crude oil on 1 kg Merck silica gel grade 60 with 20:1 heptane/ethyl acetate (90.14 g, 94.6%).

Provenance & Evidence