methyl 2-cyano-2-cyclohexylideneacetate

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

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

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: To a solution of cyano-cyclohexylidene-acetic acid methyl ester (20.0 g, 112 mmol) in acetonitrile (400 mL) was added nitromethane (30 mL, 558 mmol) followed by dropwise addition of DBU (16.9 mL, 113 mmol) over five minutes. The solution went from clear to orange and was stirred at room temperature for 5.5 hours. The solution was diluted with ether (1 L), washed with 1N HCl (2×250 mL) and then brine (2×250 mL). The organic layer was dried over sodium sulfate, filtered and evaporated. The residue was chromatographed on a wet-packed silica gel column (6.5×40 cm) eluting with 95:5 hexanes/ethyl acetate. The appropriate fractions were combined and evaporated to give 18.6 g (86%) of 1-cyano-spiro[2.5]octane-1-carboxylic acid methyl ester as a clear oil: 1H NMR (300 MHz, CDCl3) δ 1.35 (m, 1H), 1.49 (d, J=5.0 Hz, 1H), 1.5–1.75 (m, 9H), 1.82 (d, J=5.0 Hz, 1H), 3.83 (s, 3H). washed with 1N HCl (2×250 mL) The organic layer was dried over sodium sulfate filtered evaporated The residue was chromatographed on a wet-packed silica gel column (6.5×40 cm) eluting with 95:5 hexanes/ethyl acetate evaporated

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

Procedure: To a solution of cyclohexanone (84.1 g, 1 mol) in dry benzene (100 mL) was added methyl cyanoacetate (99.1 g, 1 mol), ammonium acetate (10 g) and glacial acetic acid (20 mL). The reaction mixture was heated to reflux using Dean-Stark apparatus for 12 hours and allowed to cool to room temperature. Excess of solvents was removed in vacuo and the residue was dissolved in EtOAc (400 mL). The organic layer was washed with water, dried over sodium sulfate and evaporated to give cyano-cyclohexylidene-acetic acid methyl ester as pale yellow oil. Further purification of the pale yellow oil by distillation (10 mm Hg, 150–155° C.) gave product the title compound (110 g, 61%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 1.70–1.85 (m, 6H), 2.70 (t, 2H), 3.00 (t, 2H), 3.80 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 25.9, 28.6, 28.9, 31.9, 37.2, 52.8, 101.9, 115.8, 162.7, 180.8. The reaction mixture was heated to reflux for 12 hours Excess of solvents was removed in vacuo the residue was dissolved in EtOAc (400 mL) The organic layer was washed with water dried over sodium sulfate evaporated

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

Procedure: To a solution of cyano-cyclohexylidene-acetic acid methyl ester (20.0 g, 112 mmol) in acetonitrile (400 mL) was added nitromethane (30 mL, 558 mmol) followed by dropwise addition of DBU (16.9 mL, 113 mmol) over five minutes. The solution went from clear to orange and was stirred at room temperature for 5.5 hours. The solution was diluted with ether (1 L), washed with 1N HCl (2×250 mL) and then brine (2×250 mL). The organic layer was dried over sodium sulfate, filtered and evaporated. The residue was chromatographed on a wet-packed silica gel column (6.5×40 cm) eluting with 95:5 hexanes/ethyl acetate. The appropriate fractions were combined and evaporated to give 18.6 g (86%) of 1-cyano-spiro[2.5]octane-1-carboxylic acid methyl ester as a clear oil: 1H NMR (300 MHz, CDCl3) δ 1.35 (m, 1H), 1.49 (d, J=5.0 Hz, 1H), 1.5-1.75 (m, 9H), 1.82 (d, J=5.0 Hz, 1H), 3.83 (s, 3H). washed with 1N HCl (2×250 mL) The organic layer was dried over sodium sulfate filtered evaporated The residue was chromatographed on a wet-packed silica gel column (6.5×40 cm) eluting with 95:5 hexanes/ethyl acetate evaporated

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

Procedure: To a solution of cyclohexanone (84.1 g, 1 mol) in dry benzene (100 mL) was added methyl cyanoacetate (99.1 g, 1 mol), ammonium acetate (10 g) and glacial acetic acid (20 mL). The reaction mixture was heated to reflux using Dean-Stark apparatus for 12 hours and allowed to cool to room temperature. Excess of solvents was removed in vacuo and the residue was dissolved in EtOAc (400 mL). The organic layer was washed with water, dried over sodium sulfate and evaporated to give cyano-cyclohexylidene-acetic acid methyl ester as pale yellow oil. Further purification of the pale yellow oil by distillation (10 mm Hg, 150-155° C.) gave product 15 (110 g, 61%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 1.70-1.85 (m, 6H), 2.70 (t, 2H), 3.00 (t, 2H), 3.80 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 25.9, 28.6, 28.9, 31.9, 37.2, 52.8, 101.9, 115.8, 162.7, 180.8. The reaction mixture was heated to reflux for 12 hours Excess of solvents was removed in vacuo the residue was dissolved in EtOAc (400 mL) The organic layer was washed with water dried over sodium sulfate evaporated