5,5-dimethyl-2-(2-oxopropyl)cyclohexane-1,3-dione

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An oven dried flask was charged with sodium hydride (3.61 g, 142.7 mmol) to which 200 mL of anhydrous DMF was added. The flask was cooled in an ice bath before adding 5,5-dimethyl-1,3-cyclohexanedione (20.0 g, 142.7 mmol) and chloroacetone (11.36 mL, 142.7 mmol) in 100 mL DMF in a controlled manner. The reaction was allowed to warm to RT and stirred for 3 h. Saturated NH4Cl was added and the mixture was washed several times with EtOAc. The combined organic layer was dried over MgSO4, filtered, the solvent removed in vacuo (below 40° C.). LCMS m/z M+H=197.1. An oven dried flask was added The flask was cooled in an ice bath the mixture was washed several times with EtOAc The combined organic layer was dried over MgSO4 filtered the solvent removed in vacuo (below 40° C.)

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An oven dried flask was charged with sodium hydride (3.61 g, 142.7 mmol) to which 200 mL of anhydrous DMF was added. The flask was cooled in an ice bath before adding 5,5-dimethyl-1,3-cyclohexanedione (20.0 g, 142.7 mmol) and chloroacetone (11.36 mL, 142.7 mmol) in 100 mL DMF in a controlled manner. The reaction was allowed to warm to RT and stirred for 3 h. Saturated NH4Cl was added and the mixture was washed several times with EtOAc. The combined organic layer was dried over MgSO4, filtered, the solvent removed in vacuo (below 40° C.). LCMS m/z M+H=197.1. An oven dried flask was added The flask was cooled in an ice bath the mixture was washed several times with EtOAc The combined organic layer was dried over MgSO4 filtered the solvent removed in vacuo (below 40° C.)

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An oven dried flask was charged with sodium hydride (3.61 g, 142.7 mmol) to which 200 mL of anhydrous DMF was added. The flask was cooled in an ice bath before adding 5,5-dimethyl-1,3-cyclohexanedione (20.0 g, 142.7 mmol) and chloroacetone (11.36 mL, 142.7 mmol) in 100 mL DMF in a controlled manner. The reaction was allowed to warm to RT and stirred for 3 h. Saturated NH4Cl was added and the mixture was washed several times with EtOAc. The combined organic layer was dried over MgSO4, filtered, the solvent removed in vacuo (below 40° C.). LCMS m/z M+H=197.1. An oven dried flask was added The flask was cooled in an ice bath the mixture was washed several times with EtOAc The combined organic layer was dried over MgSO4 filtered the solvent removed in vacuo (below 40° C.)

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An oven dried flask was charged with sodium hydride (3.61 g, 142.7 mmol) to which 200 mL of anhydrous DMF was added. The flask was cooled in an ice bath before adding 5,5-dimethyl-1,3-cyclohexanedione (20.0 g, 142.7 mmol) and chloroacetone (11.36 mL, 142.7 mmol) in 100 mL DMF in a controlled manner. The reaction was allowed to warm to RT and stirred for 3 h. Saturated NH4Cl was added and the mixture was washed several times with EtOAc. The combined organic layer was dried over MgSO4, filtered, the solvent removed in vacuo (below 40° C.). LCMS m/z M+H=197.1. An oven dried flask was added The flask was cooled in an ice bath the mixture was washed several times with EtOAc The combined organic layer was dried over MgSO4 filtered the solvent removed in vacuo (below 40° C.)

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude tri-ketone from Example 37 was dissolved in 300 mL of acetic acid to which ammonium acetate (55 g, 0.714 mmol) was added. The reaction mixture was heated at 65° C. until all starting material had disappeared (2-3 h), cooled to RT, added to H2O, and washed with EtOAc. The organic layer was washed with saturated NaHCO3 (×3), brine (×1) and dried over MgSO4. Solvent was removed in vacuo and the oily residue was passed through a plug of silica. The appropriate fractions were collected and solvent was removed. The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material crashing back out of solution after the addition of EtOAc will be gummy. To remedy this simply add a little EtOAc). The solid was filtered and washed with hexanes. More solid can be recovered by removing the solvent and repeating this procedure. LCMS m/z M+H=178.1. Approximately 5 g of a tan solid was collected and identified as 2,6,6-trimethyltetrahydroindol-4-one. was added (2-3 h) cooled to RT washed with EtOAc The organic layer was washed with saturated NaHCO3 (×3), brine (×1) dried over MgSO4 Solvent was removed in vacuo The appropriate fractions were collected solvent was removed The resulting solid was washed with EtOAc and hexanes (if too much hexanes is added the material after the addition of EtOAc this simply add a little EtOAc) The solid was filtered washed with hexanes More solid can be recovered by removing the solvent Approximately 5 g of a tan solid was collected

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An oven dried flask was charged with sodium hydride (3.61 g, 142.7 mmol) to which 200 mL of anhydrous DMF was added. The flask was cooled in an ice bath before adding 5,5-dimethyl-1,3-cyclohexanedione (20.0 g, 142.7 mmol) and chloroacetone (11.36 mL, 142.7 mmol) in 100 mL DMF in a controlled manner. The reaction was allowed to warm to RT and stirred for 3 h. Saturated NH4Cl was added and the mixture was washed several times with EtOAc. The combined organic layer was dried over MgSO4, filtered, the solvent removed in vacuo (below 40° C.). LCMS m/z M+H=197.1. An oven dried flask was added The flask was cooled in an ice bath the mixture was washed several times with EtOAc The combined organic layer was dried over MgSO4 filtered the solvent removed in vacuo (below 40° C.)