Bis(2-chloroethyl) ether → 2-(Tert-butyl-dimethyl-silanyloxy)-5-morpholin-4-yl-benzoic acid methyl ester

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Reaction Steps

A solution of 5-amino-2-(tert-butyl-dimethyl-silanyloxy)benzoic acid methyl ester (4.5 g, 16 mmol), 2-chloroethyl ether (1.9 mL, 16.2 mmol), and diisopropylethylamine (5.6 mL, 32.1 mmol) in DMF (50 mL) was stirred at 100° C. for 48 h. The reaction mixture was poured into 10% aqueous NaHCO3 (100 mL) and extracted with ether (200 mL). The organic layer was washed with water (5×100 mL) and brine (100 mL), dried over magnesium sulfate (MgSO4), and concentrated to a red syrup. The residue was purified by flash chromatography (silica gel, 4×15 cm, eluted with 9/1 hexanes/EtOAc) to yield 2-(tert-butyl-dimethyl-silanyloxy)-5-morpholin-4-yl-benzoic acid methyl ester (1.0 g, 18%).

Provenance & Evidence