tert-Butyldimethylsilyl chloride → 2-(T-Butyldimethylsilyloxy)-4-bromoanisole

Participants

Reaction Steps

Ethyldiisopropylamine (1.72 ml, 9.85 mmol) was added to a solution of 5-bromo-2-methoxy-phenol (0.80 g, 3.94 mmol) in DMF (10 ml) at rt. The clear, colorless solution was stirred for 5 min. followed by addition of tert-butylchlorodimethylsilane (0.71 g, 4.73 mmol). The reaction was complete in about two hours. Distilled water (˜6 ml) was added to the clear solution, stirred for 10 min., added ether (50 ml) and sat. NaHCO3 (10 ml), stirred for 30 min. The ether portion was separated and the aqueous phase was extracted with ether (2×50 ml). The combined ether phases were washed with water (100 ml), brine (60 ml), dried over MgSO4, filtered and concentrated to an oil, which was further purified by flash column chromatography [100% hexane with 0.5% triethylamine gradient to 30% EtOAc in hexane with 0.5% Et3N] to give (5-bromo-2-methoxy-phenoxy)-tert-butyl-dimethyl-silane as an oil (0.59 g, 99%), HPLC purity 99.5% at 1.43 min. (90/10 ACN/0.1% H3PO4): 1H NMR (DMSO-d6) δ 7.04-6.97(m, 2H, Ar), 6.71 (d, J=8 Hz, Ar), 3.78 (s, 3H, single OCH3), 0.99 (s, 9H, 3OCH3), 0.16 (s, 6H, 2OCH3). The product was carried over to the next step.

Provenance & Evidence