tert-Butyl acrylate → 3-(2-Formyl-4-hydroxyphenyl)acrylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-bromo-5-hydroxybenzaldehyde (200 g, 1.0 mole) in propionitrile (6 L) under N2 was added tri-o-tolyl phosphine (75.4 g, 0.25 mol) and diisopropylethylamine (350 mL, 260 g, 2.0 mol). The solution was degassed and purged with N2 three times. To this solution was added tert-butylacrylate (440 mL, 385 g, 3.0 mol) and palladium acetate trimer (27.8 g, 0.12 mol). The mixture was degassed three times and heated to 80° C. over 30 min. After 30 min, the reaction was cooled to ambient temperature and filtered. The solids were washed with acetonitrile. The filtrate was transferred to a separatory funnel with acetonitrile (4 L total) and was extracted with hexanes (4×5 L). The propionitrile/acetonitrile layer was concentrated by rotary evaporation. The residue was dissolved in toluene (4 L) and washed successively with 1N HCl (1 L), water (1 L), and brine (1 L). The organic layer was dried (Na2SO4), filtered, and concentrated to afford crude product as a wet brown solid (293 g). The crude product was dissolved in CH2Cl2 (600 mL) with stirring. To this solution was added hexanes (1.8 L) over ˜2 h, and the resulting slurry was stirred at ambient temperature for 1 h. The slurry was cooled in an ice water bath and stirred for 1 h. The product was isolated by filtration, washed with hexanes, and dried under vacuum to afford the product as a tan solid (199.5 g, 80.6%).

Provenance & Evidence