Water → Methyl 2-(4-cyanophenylamino)-2-(3-bromo-5-ethyl-4-hydroxyphenyl)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of 3-bromo-5-ethyl-4-hydroxybenzaldehyde 2 (2.90 g, 12.6 mmol), 4-aminobenzonitrile (1.64 g, 13.9 mmol), and methanol (30 mL) was maintained at room temperature for 1 h. The solution was cooled to 0° C., and tosylmethylisocyanide (2.95 g, 15.2 mmol) and BF3.Et2O (5.70 mL, 45.4 mmol) were added sequentially. The mixture was allowed to warm to room temperature over 5 h, then water (1.13 mL, 63 mmol) was added and the mixture was stirred vigorously for 12 h. The solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate (200 mL) and saturated aqueous NaHCO3 (200 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous NaHCO3 (1×100 mL), brine (1×100 mL), dried (Na2SO4), and filtered. The solution was concentrated and adsorbed onto Celite®, then purified by silica gel chromatography (SiO2, gradient elution 10–15–20% ethyl acetate/hexanes) to yield 3.8 g (77%) of methyl 2-(4-cyanophenylamino)-2-(3-bromo-5-ethyl-4-hydroxyphenyl)acetate 3 as a colorless solid.

Provenance & Evidence