2-cyclohexylidenepropanedinitrile

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

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

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

Procedure: A solution of vinylmagnesium bromide (1 M in THF, 24 mL, 24 mmol) was added dropwise over 2 min to a solution of the product from Example 145A (730 mg, 4.99 mmol) in THF (8 mL) under nitrogen. The reaction mixture was stirred at room temperature for 13 hours, then quenched by cautious addition of saturated aqueous NH4Cl (25 mL). The mixture was stirred vigorously for 10 minutes, and then diluted with water (10 mL). The aqeuous layer was separated and extracted with EtOAc (25 mL). The combined organic phase was concentrated under vacuum, and the residue was purified by flash chromatography (silica gel eluted with hexanes-EtOAc, 90:10-80:20) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.24-1.37 (m, 2H), 1.40-1.68 (m, 6H), 1.85-2.03 (m, 2H), 3.56 (s, 1H), 5.39 (d, J=17.4 Hz, 1H), 5.53 (d, J=10.7 Hz, 1H), 5.73 (dd, J=17.5, 10.7 Hz, 1H). quenched by cautious addition of saturated aqueous NH4Cl (25 mL) The mixture was stirred vigorously for 10 minutes diluted with water (10 mL) The aqeuous layer was separated extracted with EtOAc (25 mL) The combined organic phase was concentrated under vacuum the residue was purified by flash chromatography (silica gel eluted with hexanes-EtOAc, 90:10-80:20)

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

Procedure: Acetic acid was added at room temperature to a stirring mixture of malononitrile (2.65 mL, 42.1 mmol), cyclohexanone (5.03 g, 51.3 mmol) and NH4OAc (6.49 g, 84 mmol) in toluene (200 mL). The resulting mixture was heated at reflux under a Dean-Stark trap for 2 hours (6 mL water collected), then cooled to room temperature. The mixture was concentrated under vacuum, and the residue was distilled under vacuum (air bath 110-130° C./˜10 mm) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.61-1.74 (m, 2H), 1.81 (ddt, J=6.5, 6.2, 5.8 Hz, 4H), 2.66 (dd, J=6.5, 6.2 Hz, 4H). The resulting mixture was heated at reflux under a Dean-Stark trap for 2 hours (6 mL water collected) The mixture was concentrated under vacuum the residue was distilled under vacuum (air bath 110-130° C./˜10 mm)