Reaction Steps
Acetylacetone (1.9 mL, 19 mmol) was added dropwise over 30 minutes to a cooled (ice/H2O bath) suspension of 95% NaH (0.42 g, 18 mmol) in anhydrous THF (65 mL). After H2 evolution had ceased, a solution of methyl (4-bromomethyl)benzoate (4.01 g, 17.5 mmol) in anhydrous THF (9 mL) was added at once with stirring. The reaction mixture was heated to 50° C. (internal temperature) for 48 h, cooled to room temperature, and poured into saturated aqueous NH4Cl (125 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc (3×100 mL). The combined organic extracts were dried (Na2SO4). The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give an oily residue. Flash column chromatography (EtOAc:hexane (1:8)) gave 4e as a pale oil (3.78 g, 86%). 1H NMR (300 MHz, CDCl3): δ 7.95 (d, J=8.1 Hz, 2H, enol), 7.92 (d, J=8.1 Hz, 2H, keto), 7.21 (d, J=8.1 Hz, 2H, keto), 7.20 (d, J=8.1 Hz, 2H, enol), 4.00 (t, J=7.5 Hz, 1H, keto), 3.88 (s, 3H, enol), 3.87 (s, 3H, keto), 3.67 (s, 2H, enol), 3.17 (d, J=7.5 Hz, 2H, keto), 2.11 (s, 6H, keto), 2.03 (s, 6H, enol). 13C NMR (75 MHz, CDCl3): δ 203.2, 192.1, 167.1, 145.4, 143.7, 130.2, 128.9, 128.7, 127.7, 107.9, 69.7, 34.2, 33.3, 29.9, 23.5. IR (thin film, CHCl3 cm−1): 3420, 3002, 2953, 2844, 1935, 1732, 1710, 1609, 1346, 1359, 1272, 1178, 1109, 1019. MS (ESI): m/z 271 (M+Na). Anal. Calcd. for C14H16O4: C, 67.73; H, 6.50; O, 25.78. Found: C, 67.69; H, 6.48; O, 25.81.
