2-propylcyclohex-2-en-1-one

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propyl-cyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67–1.55 (m, 8H), 1.43–1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Absolute ethanol (200 mL) followed by tetrahydrofuran (50 mL) was added at −78° C. to a solution of methyl phenyl ether from step 1 (10.0 g, 66.58 mmol) suspended in anhydrous ammonia (700 mL). Lithium metal (2.3 g, 330 mmol) was added at −78° C. in small portions over 0.5 h to yield a deep blue solution. The reaction was stirred at −78° C. until a white solution resulted. The cooling bath was taken away, the flask exposed to the atmosphere, and the ammonia was removed under a stream of nitrogen. The solid residue remaining was dissolved in a minimum amount of water and acidified to pH 3 with 10% hydrochloric acid, and then extracted several times with diethyl ether. The combined ether phase was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and carefully concentrated under reduced pressure at 0° C. to provide an oil. The oil was dissolved in 10% hydrochloric acid (200 mL) and refluxed for 3 h. The reaction mixture was then cooled to room temperature and extracted several times with diethyl ether. The combined ether extracts were washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield an oil. Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate) gave 2-propylcyclohexenone (4.43 g): 1H NMR (300 MHz, CDCl3) δ 6.95–6.89 (m, 1H), 5.97 (app dt, J=10, 2 Hz, 1H), 2.39–2.36 (m, 3H), 2.20–2.04 (m, 1H), 1.88–1.63 (m, 2H), 1.50–1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H). to yield a deep blue solution resulted the ammonia was removed under a stream of nitrogen The solid residue remaining was dissolved in a minimum amount of water extracted several times with diethyl ether The combined ether phase was washed with saturated sodium chloride dried (sodium sulfate) filtered carefully concentrated under reduced pressure at 0° C. to provide an oil refluxed for 3 h The reaction mixture was then cooled to room temperature extracted several times with diethyl ether The combined ether extracts were washed with saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield an oil Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate)

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propyl-cyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67–1.55 (m, 8H), 1.43–1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Absolute ethanol (200 mL) followed by tetrahydrofuran (50 mL) was added at −78° C. to a solution of methyl phenyl ether from step 1 (10.0 g, 66.58 mmol) suspended in anhydrous ammonia (700 mL). Lithium metal (2.3 g, 330 mmol) was added at −78° C. in small portions over 0.5 h to yield a deep blue solution. The reaction was stirred at −78° C. until a white solution resulted. The cooling bath was taken away, the flask exposed to the atmosphere, and the ammonia was removed under a stream of nitrogen. The solid residue remaining was dissolved in a minimum amount of water and acidified to pH 3 with 10% hydrochloric acid, and then extracted several times with diethyl ether. The combined ether phase was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and carefully concentrated under reduced pressure at 0° C. to provide an oil. The oil was dissolved in 10% hydrochloric acid (200 mL) and refluxed for 3 h. The reaction mixture was then cooled to room temperature and extracted several times with diethyl ether. The combined ether extracts were washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield an oil. Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate) gave 2-propylcyclohexenone (4.43 g): 1H NMR (300 MHz, CDCl3) δ 6.95–6.89 (m, 1H), 5.97 (app dt, J=10, 2 Hz, 1H), 2.39–2.36 (m, 3H), 2.20–2.04 (m, 1H), 1.88–1.63 (m, 2H), 1.50–1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H). to yield a deep blue solution resulted the ammonia was removed under a stream of nitrogen The solid residue remaining was dissolved in a minimum amount of water extracted several times with diethyl ether The combined ether phase was washed with saturated sodium chloride dried (sodium sulfate) filtered carefully concentrated under reduced pressure at 0° C. to provide an oil refluxed for 3 h The reaction mixture was then cooled to room temperature extracted several times with diethyl ether The combined ether extracts were washed with saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield an oil Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate)

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propyl-cyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67–1.55 (m, 8H), 1.43–1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propylcyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67-1.55 (m, 8H), 1.43-1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Absolute ethanol (200 mL) followed by tetrahydrofuran (50 mL) was added at −78° C. to a solution of methyl phenyl ether from step 1 (10.0 g, 66.58 mmol) suspended in anhydrous ammonia (700 mL). Lithium metal (2.3 g, 330 mmol) was added at −78° C. in small portions over 0.5 h to yield a deep blue solution. The reaction was stirred at −78° C. until a white solution resulted. The cooling bath was taken away, the flask exposed to the atmosphere, and the ammonia was removed under a stream of nitrogen. The solid residue remaining was dissolved in a minimum amount of water and acidified to pH 3 with 10% hydrochloric acid, and then extracted several times with diethyl ether. The combined ether phase was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and carefully concentrated under reduced pressure at 0° C. to provide an oil. The oil was dissolved in 10% hydrochloric acid (200 mL) and refluxed for 3 h. The reaction mixture was then cooled to room temperature and extracted several times with diethyl ether. The combined ether extracts were washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield an oil. Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate) gave 2-propylcyclohexenone (4.43 g): 1H NMR (300 MHz, CDCl3) δ 6.95-6.89 (m, 1H), 5.97 (app dt, J=10, 2 Hz, 1H), 2.39-2.36 (m, 3H), 2.20-2.04 (m, 1H), 1.88-1.63 (m, 2H), 1.50-1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H). to yield a deep blue solution resulted the ammonia was removed under a stream of nitrogen The solid residue remaining was dissolved in a minimum amount of water extracted several times with diethyl ether The combined ether phase was washed with saturated sodium chloride dried (sodium sulfate) filtered carefully concentrated under reduced pressure at 0° C. to provide an oil refluxed for 3 h The reaction mixture was then cooled to room temperature extracted several times with diethyl ether The combined ether extracts were washed with saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield an oil Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate)

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propylcyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67-1.55 (m, 8H), 1.43-1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Absolute ethanol (200 mL) followed by tetrahydrofuran (50 mL) was added at −78° C. to a solution of methyl phenyl ether from step 1 (10.0 g, 66.58 mmol) suspended in anhydrous ammonia (700 mL). Lithium metal (2.3 g, 330 mmol) was added at −78° C. in small portions over 0.5 h to yield a deep blue solution. The reaction was stirred at −78° C. until a white solution resulted. The cooling bath was taken away, the flask exposed to the atmosphere, and the ammonia was removed under a stream of nitrogen. The solid residue remaining was dissolved in a minimum amount of water and acidified to pH 3 with 10% hydrochloric acid, and then extracted several times with diethyl ether. The combined ether phase was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and carefully concentrated under reduced pressure at 0° C. to provide an oil. The oil was dissolved in 10% hydrochloric acid (200 mL) and refluxed for 3 h. The reaction mixture was then cooled to room temperature and extracted several times with diethyl ether. The combined ether extracts were washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield an oil. Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate) gave 2-propylcyclohexenone (4.43 g): 1H NMR (300 MHz, CDCl3) δ 6.95-6.89 (m, 1H), 5.97 (app dt, J=10, 2 Hz, 1H), 2.39-2.36 (m, 3H), 2.20-2.04 (m, 1H), 1.88-1.63 (m, 2H), 1.50-1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H). to yield a deep blue solution resulted the ammonia was removed under a stream of nitrogen The solid residue remaining was dissolved in a minimum amount of water extracted several times with diethyl ether The combined ether phase was washed with saturated sodium chloride dried (sodium sulfate) filtered carefully concentrated under reduced pressure at 0° C. to provide an oil refluxed for 3 h The reaction mixture was then cooled to room temperature extracted several times with diethyl ether The combined ether extracts were washed with saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield an oil Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate)

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propyl-cyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67–1.55 (m, 8H), 1.43–1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Absolute ethanol (200 mL) followed by tetrahydrofuran (50 mL) was added at −78° C. to a solution of methyl phenyl ether from step 1 (10.0 g, 66.58 mmol) suspended in anhydrous ammonia (700 mL). Lithium metal (2.3 g, 330 mmol) was added at −78° C. in small portions over 0.5 h to yield a deep blue solution. The reaction was stirred at −78° C. until a white solution resulted. The cooling bath was taken away, the flask exposed to the atmosphere, and the ammonia was removed under a stream of nitrogen. The solid residue remaining was dissolved in a minimum amount of water and acidified to pH 3 with 10% hydrochloric acid, and then extracted several times with diethyl ether. The combined ether phase was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and carefully concentrated under reduced pressure at 0° C. to provide an oil. The oil was dissolved in 10% hydrochloric acid (200 mL) and refluxed for 3 h. The reaction mixture was then cooled to room temperature and extracted several times with diethyl ether. The combined ether extracts were washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield an oil. Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate) gave 2-propylcyclohexenone (4.43 g): 1H NMR (300 MHz, CDCl3) δ 6.95–6.89 (m, 1H), 5.97 (app dt, J=10, 2 Hz, 1H), 2.39–2.36 (m, 3H), 2.20–2.04 (m, 1H), 1.88–1.63 (m, 2H), 1.50–1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H). to yield a deep blue solution resulted the ammonia was removed under a stream of nitrogen The solid residue remaining was dissolved in a minimum amount of water extracted several times with diethyl ether The combined ether phase was washed with saturated sodium chloride dried (sodium sulfate) filtered carefully concentrated under reduced pressure at 0° C. to provide an oil refluxed for 3 h The reaction mixture was then cooled to room temperature extracted several times with diethyl ether The combined ether extracts were washed with saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield an oil Purification by flash column chromatography (silica, 89:11 hexanes/ethyl acetate)

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

Procedure: A solution of sodium metal (30 mg, 1.30 mmol) in absolute ethanol (4.0 mL) was stirred at −10° C. for 0.5 h. Diethyl malonate (3.5 mL, 23 mmol) was added at −10° C. followed by addition of a solution of 2-propylcyclohexenone (3.0 g, 21.7 mmol) in absolute ethanol (3.0 mL). The reaction mixture was stirred an additional 12 h at room temperature. The reaction mixture was acidified to pH 3 with 10% hydrochloric acid and then extracted several times with diethyl ether. The combined ether extracts were washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield a yellow oil. Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate) gave 2-(3-oxo-4-propylcyclohexyl)-malonic acid diethyl ester (5.07 g): 1H NMR (300 MHz, CDCl3) δ 4.21 (q, J=7 Hz, 2H), 4.20 (q, J=7 Hz, 2H), 3.30 (s, 0.5H), 3.28 (s, 0.5H), 2.67-1.55 (m, 8H), 1.43-1.11 (m, 10H), 0.90 (t, J=7 Hz, 1.5H), 0.90 (t, J=7.0 Hz, 1.5H). extracted several times with diethyl ether The combined ether extracts were washed with water, and saturated sodium chloride dried (sodium sulfate) filtered concentrated under reduced pressure to yield a yellow oil Purification by flash column chromatography (silica, 83:17 hexanes/ethyl acetate)