3-oxocyclobutane-1-carbonitrile

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Oxocyclobutanecarbonitrile was prepared according to Elend, D.; Fengas, D.; Fray, J. M. Synthetic Communications, 2005, 35, 657. To a solution of 3-oxocyclobutanecarbonitrile (600 mg, 6.31 mmol) in MeOH (25 mL) at 0° C. was slowly added sodium borohydride (263 mg, 6.94 mmol). The reaction mixture was stirred at 0° C. for 1 h then quenched with water and brine and extracted with EtOAc (3×). The combined organics were dried over MgSO4 and concentrated to afford 500 mg (82%) of cis-3-hydroxy-cyclobutanecarbonitrile as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 4.26 (quin, J=7.5 Hz, 1H), 2.70-2.82 (m, 2H), 2.50-2.66 (m, 1H), 2.26-2.41 (m, 2H), 2.09 (br. s., 1H). at 0° C. then quenched with water and brine extracted with EtOAc (3×) The combined organics were dried over MgSO4 concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Oxocyclobutanecarbonitrile was prepared according to Elend, D.; Fengas, D.; Fray, J. M. Synthetic Communications, 2005, 35, 657. To a solution of 3-oxocyclobutanecarbonitrile (600 mg, 6.31 mmol) in MeOH (25 mL) at 0° C. was slowly added sodium borohydride (263 mg, 6.94 mmol). The reaction mixture was stirred at 0° C. for 1 h then quenched with water and brine and extracted with EtOAc (3×). The combined organics were dried over MgSO4 and concentrated to afford 500 mg (82%) of cis-3-hydroxy-cyclobutanecarbonitrile as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 4.26 (quin, J=7.5 Hz, 1H), 2.70-2.82 (m, 2H), 2.50-2.66 (m, 1H), 2.26-2.41 (m, 2H), 2.09 (br. s., 1H). at 0° C. then quenched with water and brine extracted with EtOAc (3×) The combined organics were dried over MgSO4 concentrated

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of lithium (Z)-1-(5-bromo-2-methoxypyridin-3-yl)-2-(dimethoxyphosphoryl)ethenolate (2.0 g, 5.8 mmol) and 3-oxocyclobutanecarbonitrile (1.1 g, 12 mmol) in p-dioxane (6 ml) was heated at 120° C. by Microwave in 1 h. The mixture was cooled, taken up in H2O, extracted with EtOAc (3×), dried over MgSO4, concentrated to provide the title compound. MS (m+1): 307.0. The mixture was cooled extracted with EtOAc (3×) dried over MgSO4 concentrated

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of lithium (Z)-1-(5-bromo-2-methoxypyridin-3-yl)-2-(dimethoxyphosphoryl)ethenolate (2.0 g, 5.8 mmol) and 3-oxocyclobutanecarbonitrile (1.1 g, 12 mmol) in p-dioxane (6 ml) was heated at 120° C. by Microwave in 1 h. The mixture was cooled, taken up in H2O, extracted with EtOAc (3×), dried over MgSO4, concentrated to provide the title compound. MS (m+1): 307.0. The mixture was cooled extracted with EtOAc (3×) dried over MgSO4 concentrated

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of lithium (Z)-1-(5-bromo-2-methoxypyridin-3-yl)-2-(dimethoxyphosphoryl)ethenolate (2.0 g, 5.8 mmol) and 3-oxocyclobutanecarbonitrile (1.1 g, 12 mmol) in p-dioxane (6 ml) was heated at 120° C. by Microwave in 1 h. The mixture was cooled, taken up in H2O, extracted with EtOAc (3×), dried over MgSO4, concentrated to provide the title compound. MS (m+1): 307.0. The mixture was cooled extracted with EtOAc (3×) dried over MgSO4 concentrated

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of lithium (Z)-1-(5-bromo-2-methoxypyridin-3-yl)-2-(dimethoxyphosphoryl)ethenolate (2.0 g, 5.8 mmol) and 3-oxocyclobutanecarbonitrile (1.1 g, 12 mmol) in p-dioxane (6 ml) was heated at 120° C. by Microwave in 1 h. The mixture was cooled, taken up in H2O, extracted with EtOAc (3×), dried over MgSO4, concentrated to provide the title compound. MS (m+11): 307.0. The mixture was cooled extracted with EtOAc (3×) dried over MgSO4 concentrated

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of lithium (Z)-1-(5-bromo-2-methoxypyridin-3-yl)-2-(dimethoxyphosphoryl)ethenolate (2.0 g, 5.8 mmol) and 3-oxocyclobutanecarbonitrile (1.1 g, 12 mmol) in p-dioxane (6 ml) was heated at 120° C. by Microwave in 1 h. The mixture was cooled, taken up in H2O, extracted with EtOAc (3×), dried over MgSO4, concentrated to provide the title compound. MS (m+11): 307.0. The mixture was cooled extracted with EtOAc (3×) dried over MgSO4 concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Oxocyclobutanecarbonitrile was prepared according to Elend, D.; Fengas, D.; Fray, J. M. Synthetic Communications, 2005, 35, 657. To a solution of 3-oxocyclobutanecarbonitrile (600 mg, 6.31 mmol) in MeOH (25 mL) at 0° C. was slowly added sodium borohydride (263 mg, 6.94 mmol). The reaction mixture was stirred at 0° C. for 1 h then quenched with water and brine and extracted with EtOAc (3×). The combined organics were dried over MgSO4 and concentrated to afford 500 mg (82%) of cis-3-hydroxy-cyclobutanecarbonitrile as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 4.26 (quin, J=7.5 Hz, 1H), 2.70-2.82 (m, 2H), 2.50-2.66 (m, 1H), 2.26-2.41 (m, 2H), 2.09 (br. s., 1H). at 0° C. then quenched with water and brine extracted with EtOAc (3×) The combined organics were dried over MgSO4 concentrated

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 1 M of potassium tert-butoxide in THF (67.4 mL) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (11.4 mL, 0.0706 mol) in tetrahydrofuran (100 mL, 1 mol). The reaction mixture was warmed up to room temperature and cooled to 0° C. again. To the resulting mixture, a solution of 3-oxocyclobutanecarbonitrile (6.10 g, 0.0641 mol) in tetrahydrofuran (20 mL, 0.2 mol) was added. The reaction mixture was allowed to warm up to room temperature and stirred for 2 hours. After quenching with water, the mixture was extracted with EtOAc. The combined organic layers were dried and concentrated. The residue was purified by flash silica gel column, eluting with 0-10% MeOH/dichloromethane to give the titled product (5.40 g, 71.26%). LCMS (M+Na) 141.3. 1H NMR (400 MHz, CDCl3): δ 5.30 (1H, m), 3.40 (2H, m), 3.14 (3H, m) ppm. cooled to 0° C. again to warm up to room temperature After quenching with water the mixture was extracted with EtOAc The combined organic layers were dried concentrated The residue was purified by flash silica gel column eluting with 0-10% MeOH/dichloromethane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of lithium (Z)-1-(5-bromo-2-methoxypyridin-3-yl)-2-(dimethoxyphosphoryl)ethenolate (2.0 g, 5.8 mmol) and 3-oxocyclobutanecarbonitrile (1.1 g, 12 mmol) in p-dioxane (6 ml) was heated at 120° C. by Microwave in 1 h. The mixture was cooled, taken up in H2O, extracted with EtOAc (3×), dried over MgSO4, concentrated to provide the title compound. MS (m+1): 307.0. The mixture was cooled extracted with EtOAc (3×) dried over MgSO4 concentrated