Ethyl phenylacetate → Phenylacetaldehyde

Participants

Reaction Steps

To a solution of 10 g of ethyl phenylacetate in 100 mL of dry toluene cooled to −78° C. under nitrogen was added drop-wise 68 mL of 0.9 M di-isobutyl-aluminum hydride in toluene, keeping the internal temperature below −68° C. When the addition was complete, the reaction was quenched with 200 mL of 10% HCl, and extracted into 2×100 mL portions of ether. The combined ether layers were washed with 2×100 mL portions of 10% HCl, 100 mL of saturated sodium bicarbonate, diluted with 100 mL of toluene, and dried over magnesium sulfate. Concentration under reduced pressure gave 7.1 g of phenyl acetaldehyde as a volatile liquid. 1H NMR (400 MHz, CDCl3) 9.8 (s, 1H), 7.5-7.2 (m, 5H), 3.7 (s 2H). To a stirred mixture of 10 g of trans-2-(4-(tert-butyl-dimethyl-silyloxy-cyclohexyl)-isoindole-1,3-dione (Compound 2), 150 mL of anhydrous acetonitrile, 7 mL of triethylsilane and 0.7 g of bismuth tribromide was added 5 g of the freshly prepared phenyl acetaldehyde slowly keeping the temperature at or below 25° C. by means of a cooling bath. After stirring for 2 h, the reaction was quenched with 50 mL of saturated sodium bicarbonate and extracted with 3×150 mL portions of ethyl acetate. The combined extracts were dried over magnesium sulfate and concentrated under reduced pressure. Chromatography over silica gel eluting with a gradient of 2%-25% ethyl acetate in hexane gave 9.0 g of product as a white crystalline solid: 1H NMR (400 MHz, CDCl3) 7.8 (m, 2H), 7.7 (m, 2H), 7.3-7.1 (m, 5H), 4.15 (m, 1H), 3.7 (t, 2H), 3.38 (m, 1H), 2.9 (t, 2H), 2.22 (d, 2H), 2.3 (dd, 2H), 2.18 (d, 2H), 1.78 (d, 2H), 1.4 (dd, 2H).

Provenance & Evidence