Org Prep Daily

November 20, 2010

2-acetyl-3-ethoxyacrylic acid ethyl ester (E/Z)

Filed under: procedures — milkshake @ 7:13 pm

A mixture of ethyl acetoacetate 52.0g (399 mmol), ethyl orthoformate 59.2g (399 mmol) and acetic anhydride 81.6g (800 mmol) in a 0.5L round flask was refluxed under nitrogen on a 150 C oil bath for 90 min. The reflux condenser was replaced with a shortpath distillation apparatus and the formed ethyl acetate was distilled out from the reaction mixture at atmospheric pressure under nitrogen from a 150C oil bath. (This took additional one hour). The cooled reaction mixture was then distilled at 6 Torr from an oil bath (30 C to 90 C) to remove the formed acetic acid. The distillation residue was then fractionally distilled on highvac. After a small fruity-smelling front fraction (few mL) the desired product distilled at 75-82 C/0.25 Torr.

The obtained main fraction of the product was re-distilled on highvac, b.p. 80 C/0.15 Torr. Y = 48.2g of a colorless slightly oily liquid. The pure product has only a faint (non-fruity) odor.

1H-NMR (CDCl3, 400MHz) shows two sets of closely-spaced signals of the E and Z isomers, approximately of equal height:  7.671(s, 0.5H), 7.639(s, 0.5H), 4.251(m, 4H), 2.407(s, 1.5H), 2.346(s, 1.5H), 1.402(m, 3H), 1.339(m, 6H)

Note: A condensation of this material (2.5 mmol) with the diaminotriazole (2.0 mmol) from the preceding experimental in AcOH 5 mL at RT (10 min) and then at 110 C (for one hour) followed by evaporation and precipitation of the residue with MeCN provided the following cyclization product in 76% Y.
1H(d6-DMSO, 400MHz): 10.353 (s, 1H), 9.010(s, 1H), 7.774(app d, 8.8Hz, 2H), 7.423(app d, 8.8 Hz, 2H), 4.370(q, 7.1Hz, 2H), 3.084(s, 3H), 2.976(s, 6H), 1.368(t, 7.1Hz, 3H)

November 4, 2010

beta ketoester cyclization with aminotriazoles

Filed under: procedures — milkshake @ 11:02 am

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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.

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