O-Alkylation of Salicylaldehyde with Ethyl Bromoacetate and Subsequent Dehydrative AnnulationO-Alkylation of Salicylaldehyde with Ethyl Bromoacetate and Subsequent Dehydrative Annulation
SyntheticPage 703
Published Dec 04, 2013
To a 1000 mL round bottom flask equipped with large stirbar was added salicylaldehyde (15.26 g, 125 mmol, 1 equiv), MeCN (830 mL, ≈ 0.15 M in the aldehyde), and K2CO3 (51.82 g, 375 mmol, 3 equiv). The solution rapidly became yellow and was stirred for five minutes. After this time, the α-bromo ester1 (25.05 g, 150 mmol, 1.2 equiv) was added all at once, causing the solution to become colorless. The flask was then equipped with a reflux condenser and heated to reflux for 72 h while being vigorously stirred. After this time, the flask was cooled to room temperature and the solids were removed by filtration through a coarse2 fritted funnel. The solids were washed thoroughly with Et2O (250 mL) and the filtrate was transferred to a separatory funnel. Deionized water (≈ 500 mL) was added and the layers were separated. The aqueous layer was extracted with Et2O (2 x 150 mL). The combine ether layers were washed with deionized water (2 x 200 mL), followed by brine (200 mL). The organic layer was dried with Na2SO4 and the solvent was removed3 in vacuo to give the desired ester (14.89 g, 63 %) as a clear yellow-orange oil.4