Diethyl Malonate → Diethyl (1-benzhydryl-3-azetidinyl)malonate

Participants

Reaction Steps

To a suspension of sodium hydride (4.97 g, 0.129 mol) in 130 mL of anhydrous dimethyl formamide was added diethyl malonate (22.7 mL, 0.142 mol) dropwise at 0° C. and this reaction mixture was stirred at room temperature for 2 h. 1-Benzhydryl-3-(toluene-4-sulfonyl)-azetidine was added to it dropwise at 0° C. and reaction mixture was refluxed at 110° C. for 20 h. Excess sodium hydride was quenched with ammonium chloride, DMF was removed, and the reaction mixture was partitioned between chloroform and water; the aqueous layer was extracted with chloroform, the solvent was removed in vacuo, and purification by (neutral alumina) chromatography and 30% ethyl acetate/hexanes as eluent provided 2-(1-benzhydryl-azetidin-3-yl)-malonic acid diethyl ester. 1H-NMR (400 MHz, CDCl3), δ ppm 7.41-7.17 (m, 10H), 4.34 (s, 1H), 4.25-4.09 (m, 3H), 3.66 (d, 1H, J=3.66 Hz), 3.41-3.37 (m, 2H), 3.07-2.99 (m, 1H), 2.93-2.90 (m, 2H), 1.25-1.23 (m, 6H)

Provenance & Evidence