The diaminotriazole.THF from the previous step, 637mg (2.0 mmol) was dissolved in acetic acid 5 mL. Cyclohexanone-2-carboxylic acid ethyl ester 0.48mL (3 mmol) was added and the mixture was stirred at reflux on a 130C oil bath for 90 min. The cooled reaction mixture was evaporated to dryness and the oily residue was suspended in acetonitrile 5mL with sonication. The crystalline precipitate was collected by filtration, washed with acetonitrile, then dried by suction and on highvac. Y=664.5mg of a white crystalline solid (94%Y)
1H(dDMSO, 400MHz): 12.70(br s, 1H), 9.80(s, 1H), 7.69(dt, d: 8.6Hz, t:1.8Hz; 2H), 7.38(dt, d:8.8Hz, t:2.0Hz, 2H), 2.97(s, 6H), 2.61(br t, 5.7Hz, 2H), 2.40(br t, 5.9Hz, 2H), 1.72(m, 4H)
Note: Using the same reaction conditions, ethyl acetoacetate provided 92% Y of a cyclization product. Cyclopentanone-2-carboxylic acid ethyl ester gave 55.5 %Y (the product in this case crystallized directly from the reaction mixture – and it was washed with AcOH and then MeCN). The products were isomerically pure, by 1H-NMR and HPLC.