2,2-dimethylcyclohexan-1-one

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 lithium bis(trimethylsilyl)amide (1.0 M/THF, 2 eq. 13.6 mL) in THF (15 mL) was added 2,2-dimethylcyclohexanone (1.88 mL, 13.6 mmol) at −78° C. The reaction was stirred for 15 minutes, and then the intermediate obtained in Step A (3 g, 11.4 mmol) was added dropwise. The reaction was stirred overnight and allowed to warm to room temperature. To the crude product was added acetic add (19.4 mL), ammonium acetate (2.62 g, 34.0 mmol) and copper acetate (5.14 g, 28.3 mmol). The reaction mixture was heated at 100° C. and the THF was removed by distillation. The reaction was heated to 130° C. and allowed to reflux for 24 hours. Ethyl acetate (100 mL) was added and washed with sodium bicarbonate (2×30 mL), water (2×20 mL), brine (2×20 mL), dried with MgSO4, filtered, and concentrated to afford an oil. Flash chromatography (5% ethyl acetate/hexane) afforded a white solid (1.36, 3.7 mmol, 32%). 1H NMR (300 MHz, CDCl3): δ 7.17 (m, 2H), 7.08 (m, 2H), 3.98 (q, J=7.4 Hz, 2H), 3.03 (septet, J=7.0 Hz, 1H), 2.35 (t, J=5.9 Hz, 2H), 1.70 (m, 4H), 1.36 (s, 6H), 1.31 (d, J=4.1 Hz, 6H), 0.965 (t, J=7.4 Hz, 3H). FAB-MS: calculated for (C23H28FNO) 369, found 370 (M+H. mp 124-126° C. Rf=0.6 (50% CH2Cl2/hexane). The reaction was stirred overnight The reaction mixture was heated at 100° C. the THF was removed by distillation The reaction was heated to 130° C. to reflux for 24 hours Ethyl acetate (100 mL) was added washed with sodium bicarbonate (2×30 mL), water (2×20 mL), brine (2×20 mL) dried with MgSO4 filtered concentrated to afford an oil

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 500 mL round-bottomed flask was added diisopropylamine (3.5 mL) in ether (200 mL). After cooling to −30° C., butyllithium (16 mL) (1.6M in hexane) was added slowly. After stirring 30 minutes, the temperature was cooled to −5° C. 2,2-Dimethylcyclohexanone (3 g) was added slowly. The mixture was warmed up to 0° C. and stirred for 1 hour. After cooling to −5° C., hexamethylphosphoramide (8 mL) and ethyl carbonocyanidate (2.5 mL) were added. After stirring at −5° C. for 20 minutes, and warming to room temperature, the reaction was stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined the organic layers were washed with saturated aqueous NH4Cl (3×20 mL). After drying over Na2SO4, the mixture was filtered and the filtrate was concentrated. The crude product was purified by flash chromatography on silica with 0-10% ethyl acetate in hexanes to provide the title compound. the temperature was cooled to −5° C The mixture was warmed up to 0° C. stirred for 1 hour After cooling to −5° C. After stirring at −5° C. for 20 minutes warming to room temperature the reaction was stirred for 1 hour the layers were separated The aqueous layer was extracted with ether (3×20 mL) were washed with saturated aqueous NH4Cl (3×20 mL) After drying over Na2SO4 the mixture was filtered the filtrate was concentrated The crude product was purified by flash chromatography on silica with 0-10% ethyl acetate in hexanes

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 500 mL round-bottomed flask was added diisopropylamine (3.5 mL) in ether (200 mL). After cooling to −30° C., butyllithium (16 mL) (1.6M in hexane) was added slowly. After stirring 30 minutes, the temperature was cooled to −5° C. 2,2-Dimethylcyclohexanone (3 g) was added slowly. The mixture was warmed up to 0° C. and stirred for 1 hour. After cooling to −5° C., hexamethylphosphoramide (8 mL) and ethyl carbonocyanidate (2.5 mL) were added. After stirring at −5° C. for 20 minutes, and warming to room temperature, the reaction was stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined the organic layers were washed with saturated aqueous NH4Cl (3×20 mL). After drying over Na2SO4, the mixture was filtered and the filtrate was concentrated. The crude product was purified by flash chromatography on silica with 0-10% ethyl acetate in hexanes to provide the title compound. the temperature was cooled to −5° C The mixture was warmed up to 0° C. stirred for 1 hour After cooling to −5° C. After stirring at −5° C. for 20 minutes warming to room temperature the reaction was stirred for 1 hour the layers were separated The aqueous layer was extracted with ether (3×20 mL) were washed with saturated aqueous NH4Cl (3×20 mL) After drying over Na2SO4 the mixture was filtered the filtrate was concentrated The crude product was purified by flash chromatography on silica with 0-10% ethyl acetate in hexanes

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 500 mL round-bottomed flask was added diisopropylamine (3.5 mL) in ether (200 mL). After cooling to −30° C., butyllithium (16 mL) (1.6M in hexane) was added slowly. After stirring 30 minutes, the temperature was cooled to −5° C. 2,2-Dimethylcyclohexanone (3 g) was added slowly. The mixture was warmed up to 0° C. and stirred for 1 hour. After cooling to −5° C., hexamethylphosphoramide (8 mL) and ethyl carbonocyanidate (2.5 mL) were added. After stirring at −5° C. for 20 minutes, and warming to room temperature, the reaction was stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined the organic layers were washed with saturated aqueous NH4Cl (3×20 mL). After drying over Na2SO4, the mixture was filtered and the filtrate was concentrated. The crude product was purified by flash chromatography on silica with 0-10% ethyl acetate in hexanes to provide the title compound. the temperature was cooled to −5° C The mixture was warmed up to 0° C. stirred for 1 hour After cooling to −5° C. After stirring at −5° C. for 20 minutes warming to room temperature the reaction was stirred for 1 hour the layers were separated The aqueous layer was extracted with ether (3×20 mL) were washed with saturated aqueous NH4Cl (3×20 mL) After drying over Na2SO4 the mixture was filtered the filtrate was concentrated The crude product was purified by flash chromatography on silica with 0-10% ethyl acetate in hexanes

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

Procedure: The alkylation of 2-methylcyclohexanone with 1-iodopropane takes place in a manner similar to that described above for the preparation of 2,2-dimethyl-cyclohexanone.

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

Procedure: The alkylation of 2-methylcyclohexanone with 1-iodo-2-methyl-propane takes place in a manner similar to that described above for the preparation of 2,2-dimethyl-cyclohexanone.

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

Procedure: The alkylation of 2-methylcyclohexanone with ethyl iodide takes place in a manner similar to that described above for the preparation of 2,2-dimethyl-cyclohexanone.

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

Procedure: The bromination of 2,2-dimethyl-cyclohexanone takes place in a manner similar to that described above for the preparation of 2-bromo-4-isopropyl-cyclohexanone. The title compound is reacted as a crude product without further characterization.

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

Procedure: A suspension of potassium hydride (5.5 mmol) and 2-methylcyclohexanone (5 mmol) in dry tetrahydrofuran (10 ml) is stirred for 30 mins at room temperature. Triethylborane (6.25 mmol) is slowly added dropwise and the mixture is stirred for 16 hours at room temperature. After addition of methyl iodide stirring is continued for another 8 hours, the reaction is then quenched with saturated aqueous ammonium chloride solution and twice extracted with diethyl ether. The combined organic phases are dried over sodium sulphate and concentrated to dryness in a vacuum and produce the title compound, which can be reacted without [without] purification (JACS 1985, 107, 19, 5391-5396). the mixture is stirred for 16 hours at room temperature is continued for another 8 hours the reaction is then quenched with saturated aqueous ammonium chloride solution twice extracted with diethyl ether The combined organic phases are dried over sodium sulphate concentrated to dryness in a vacuum