2-methylcyclopentane-1,3-dione

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:

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

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

Procedure: The published procedure was followed. (Agosta, W. C.; Smith, A. B. J. Org. Chem. 1970, 35, 3856) A mixture of 2-methyl-1,3-cyclopentanedione (10.025 g, 89.4 mmol, Aldrich), methyl iodide (6.0 mL, 96.4 mmol, Aldrich), and KOH (5.097 g, 90.8 mmol) in H2O (25 mL)/dioxane (75 mL) was heated at reflux. After 5 h, a solution of KOH (2 g) and MeI (2.4 mL) in H2O (5 mL)/dioxane (15 mL) was added and after another 3 h at reflux the solution was allowed to stir at room temperature overnight. In the morning, the reaction was continued by addition of a solution of KOH (2 g) and MeI (2.4 mL) in H2O (5 mL)/dioxane (15 mL) and heating at reflux. After 4 h, the mixture was allowed to cool to room temperature and was extracted with ether (1×100 mL, 3×75 mL). The combined ether extracts were evaporated, the residue combined with HCl (50 mL 10%), and the resulting mixture was placed in a 120° C. oil bath until boiling was observed (ca. 15 min.). The mixture was then allowed to cool to room temperature, was neutralized by addition of NaHCO3 solution (150 mL, saturated) and the resulting mixture then extracted with CH2Cl2 (4×75 mL). The combined CH2Cl2 solution was dried (MgSO4), filtered and evaporated to leave a brown oil (10.474 g, 83 mmol, 93%) which was used directly in the next step. was heated at reflux at reflux the solution heating at reflux After 4 h to cool to room temperature was extracted with ether (1×100 mL, 3×75 mL) The combined ether extracts were evaporated was placed in a 120° C. (ca. 15 min.) to cool to room temperature was neutralized by addition of NaHCO3 solution (150 mL, saturated) the resulting mixture then extracted with CH2Cl2 (4×75 mL) The combined CH2Cl2 solution was dried (MgSO4) filtered evaporated

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

Procedure: Synthesized according to Agosta and Smith, J. Org. Chem. 35: 3856 (1970) A mixture of 2-methyl-1,3-cyclopentanedione (10.025 g, 89.4 mmol, Aldrich), methyl iodide (6.0 mL, 96.4 mmol, Aldrich), and KOH (5.097 g, 90.8 mmol) in water (25 mL)/dioxane (75 mL) was heated at reflux. After 5 hours, a solution of KOH (2 g) and MeI (2.4 mL) in water (5 mL)/dioxane (15 mL) was added and after another 3 hours at reflux, the solution was stirred at room temperature overnight. A solution of KOH (2 g) and MeI (2.4 mL) in water (5 mL)/dioxane (15 mL) was added to the overnight reaction and heating at reflux. After 4 hours, the mixture was cooled to room temperature and extracted with ether (1×100 mL, 3×75 mL). The combined ether extracts were evaporated, the residue combined with 10% HCl (50 mL), and the resulting mixture placed in a 120° C. oil bath until it began boiling (ca. 15 minutes). The mixture was cooled to room temperature, neutralized by addition of saturated NaHCO3 solution (150 mL) and the resulting mixture extracted with CH2Cl2 (4×75 mL). The combined CH2Cl2 solution was dried (MgSO4), filtered and evaporated to leave a brown oil (10.474 g, 83 mmol, 93%) which was used directly in the next step. Synthesized was heated at reflux at reflux heating at reflux After 4 hours the mixture was cooled to room temperature extracted with ether (1×100 mL, 3×75 mL) The combined ether extracts were evaporated placed in a 120° C. (ca. 15 minutes) The mixture was cooled to room temperature neutralized by addition of saturated NaHCO3 solution (150 mL) the resulting mixture extracted with CH2Cl2 (4×75 mL) The combined CH2Cl2 solution was dried (MgSO4) filtered evaporated

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 60 mL of dimethyl sulfoxide was dissolved 3.0 g of 3,6-dichloro-2-pyrazinecarbonitrile. After adding 3.0 g of potassium fluoride, the mixture thus obtained was stirred at 90-100° C. for 2 hours. The reaction mixture was returned to room temperature, to which were successively added 2.1 g of 2-methyl-1,3-cyclopentandione and 7.2 ml of triethylamine. The mixture thus obtained was stirred at room temperature for one hour. The reaction mixture was added to a mixture of 50 mL of ethyl acetate and 200 mL of water, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=2:1] to obtain 1.7 g of 6-fluoro-3-[(2-methyl-3-oxo-1-cyclopenten-1-yl)oxy]-2pyrazinecarbonitrile as a yellow-colored solid product. the mixture thus obtained was returned to room temperature, to which The mixture thus obtained was stirred at room temperature for one hour the organic layer was separated The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride dried on anhydrous magnesium sulfate the solvent was removed under reduced pressure The residue thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=2:1]

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

Procedure: Synthesized according to Agosta and Smith, J. Org. Chem. 35: 3856 (1970) A mixture of 2-methyl-1,3-cyclopentanedione (10.025 g, 89.4 mmol, Aldrich), methyl iodide (6.0 mL, 96.4 mmol, Aldrich), and KOH (5.097 g, 90.8 mmol) in water (25 mL)/dioxane (75 mL) was heated at reflux. After 5 hours, a solution of KOH (2 g) and MeI (2.4 mL) in water (5 mL)/dioxane (15 mL) was added and after another 3 hours at reflux, the solution was stirred at room temperature overnight. A solution of KOH (2 g) and MeI (2.4 mL) in water (5 mL)/dioxane (15 mL) was added to the overnight reaction and heating at reflux. After 4 hours, the mixture was cooled to room temperature and extracted with ether (1×100 mL, 3×75 mL). The combined ether extracts were evaporated, the residue combined with 10% HCl (50 mL), and the resulting mixture placed in a 120° C. oil bath until it began boiling (ca. 15 minutes). The mixture was cooled to room temperature, neutralized by addition of saturated NaHCO3 solution (150 mL) and the resulting mixture extracted with CH2Cl2 (4×75 mL). The combined CH2Cl2 solution was dried (MgSO4), filtered and evaporated to leave a brown oil (10.474 g, 83 mmol, 93%) which was used directly in the next step. Synthesized was heated at reflux at reflux heating at reflux After 4 hours the mixture was cooled to room temperature extracted with ether (1×100 mL, 3×75 mL) The combined ether extracts were evaporated placed in a 120° C. (ca. 15 minutes) The mixture was cooled to room temperature neutralized by addition of saturated NaHCO3 solution (150 mL) the resulting mixture extracted with CH2Cl2 (4×75 mL) The combined CH2Cl2 solution was dried (MgSO4) filtered evaporated

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

Procedure: Synthesized according to Agosta and Smith, J. Org. Chem., 35: 3856 (1970). A mixture of 2-methyl-1,3-cyclopentanedione (10.025 g, 89.4 mmol, Aldrich), methyl iodide (6.0 mL, 96.4 mmol, Aldrich), and KOH (5.097 g, 90.8 mmol) in water (25 mL)/dioxane (75 mL) was heated at reflux. After 5 hours, a solution of KOH (2 g) and Mel (2.4 mL) in water (5 mL)/dioxane (15 mL) was added and after another 3 hours at reflux, the solution was stirred at room temperature overnight. A solution of KOH (2 g) and Mel (2.4 mL) in water (5 mL)/dioxane (15 mL) was added to the overnight reaction and heating at reflux. After 4 hours, the mixture was cooled to room temperature and extracted with ether (1×100 mL, 3×75 mL). The combined ether extracts were evaporated, the residue combined with 10% HCl (50 mL), and the resulting mixture placed in a 120° C. oil bath until it began boiling (ca. 15 minutes). The mixture was cooled to room temperature, neutralized by addition of saturated NaHCO3 solution (150 mL) and the resulting mixture extracted with CH2Cl2 (4×75 mL). The combined CH2Cl2 solution was dried (MgSO4), filtered and evaporated to leave a brown oil (10.474 g, 83 mmol, 93%) which was used directly in the next step. Synthesized was heated at reflux at reflux heating at reflux After 4 hours the mixture was cooled to room temperature extracted with ether (1×100 mL, 3×75 mL) The combined ether extracts were evaporated placed in a 120° C. (ca. 15 minutes) The mixture was cooled to room temperature neutralized by addition of saturated NaHCO3 solution (150 mL) the resulting mixture extracted with CH2Cl2 (4×75 mL) The combined CH2Cl2 solution was dried (MgSO4) filtered evaporated

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

Procedure: Synthesized according to Agosta and Smith, J. Org. Chem., 35: 3856 (1970). A mixture of 2-methyl-1,3-cyclopentanedione (10.025 g, 89.4 mmol, Aldrich), methyl iodide (6.0 mL, 96.4 mmol, Aldrich), and KOH (5.097 g, 90.8 mmol) in water (25 mL)/dioxane (75 mL) was heated at reflux. After 5 hours, a solution of KOH (2 g) and MeI (2.4 mL) in water (5 mL)/dioxane (15 mL) was added and after another 3 hours at reflux, the solution was stirred at room temperature overnight. A solution of KOH (2 g) and MeI (2.4 mL) in water (5 mL)/dioxane (15 mL) was added to the overnight reaction and heating at reflux. After 4 hours, the mixture was cooled to room temperature and extracted with ether (1×100 mL, 3×75 mL). The combined ether extracts were evaporated, the residue combined with 10% HCl (50 mL), and the resulting mixture placed in a 120° C. oil bath until it began boiling (ca. 15 minutes). The mixture was cooled to room temperature, neutralized by addition of saturated NaHCO3 solution (150 mL) and the resulting mixture extracted with CH2Cl2 (4×75 mL). The combined CH2Cl2 solution was dried (MgSO4), filtered and evaporated to leave a brown oil (10.474 g, 83 mmol, 93%) which was used directly in the next step. Synthesized was heated at reflux at reflux heating at reflux After 4 hours the mixture was cooled to room temperature extracted with ether (1×100 mL, 3×75 mL) The combined ether extracts were evaporated placed in a 120° C. (ca. 15 minutes) The mixture was cooled to room temperature neutralized by addition of saturated NaHCO3 solution (150 mL) the resulting mixture extracted with CH2Cl2 (4×75 mL) The combined CH2Cl2 solution was dried (MgSO4) filtered evaporated