ethyl 2-cyano-2-cyclohexylideneacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1 M Benzylmagnesium chloride in diethyl ether (18.92 ml) was added dropwise to ethyl 2-cyano-2-cyclohexylideneacetate (1.828 g, 9.46 mmol) in diethyl ether (6.31 ml) at 23° C. The mixture was stirred at room temperature for 3 days. Then 10% hydrochloric acid (7.83 ml, 255 mmol) was added dropwise at 0° C. while stirring. The organic layer was separated, washed with water, dried over Na2SO4, filtered, and concentrated. while stirring The organic layer was separated washed with water dried over Na2SO4 filtered concentrated

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of cyclohexanone (1.50 ml, 14.47 mmol) in toluene (24.12 ml) was added ethyl cyanoacetate (1.556 ml, 14.62 mmol), acetic acid (0.166 ml, 2.89 mmol), and ammonium acetate (0.112 g, 1.447 mmol). The mixture was heated to a reflux at 150° C. in a Dean-Stark apparatus. After 5 h, the reaction was cooled and washed with water and saturated NaHCO3 solution. The organics were dried over Na2SO4, filtered, and concentrated. The mixture was heated to the reaction was cooled washed with water and saturated NaHCO3 solution The organics were dried over Na2SO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of cyano-cyclohexylidene-acetic acid ethyl ester (1.37 g, 7.09 mmol) in 30 mL acetonitrile was added nitromethane (1.92 mL, 35.5 mmol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (1.06 mL, 7.09 mmol) resulting in an orange solution. The reaction was stirred for 2.5 hours, then partitioned between ethyl ether (Et2O) and 1N hydrochloric acid (HCl) (aq). The phases were separated, and the organic phase washed with brine, dried over magnesium sulfate (MgSO4), and concentrated. Flash chromatography of the residue (5% ethyl acetate (EtOAc)/hexanes) afforded 1.1 g (75%) of 1-cyano-spiro[2.5]octane-1-carboxylic acid ethyl ester as a colorless oil. 1H NMR (CDCl3) δ 4.22 (m, 2H), 1.77 (d, J=5.1 Hz, 1H), 1.42–1.72 (m, 10H), 1.40 (d, J=5.1 Hz, 1H), 1.30 (t, J=7.1 Hz, 3H). 13C NMR δ 166.40, 118.60, 62.72, 40.20, 34.67, 29.01, 28.75, 25.69, 25.54, 25.28, 24.66, 14.38. LRMS: m/z 208.0 (M+1). IR: 2239, 1732 cm−1. Anal. Calcd for C12H17NO2: C, 69.54; H, 8.27; N, 6.76. Found: C, 69.41; H, 8.33; N, 6.75. resulting in an orange solution partitioned between ethyl ether (Et2O) and 1N hydrochloric acid (HCl) (aq) The phases were separated the organic phase washed with brine dried over magnesium sulfate (MgSO4) concentrated