3-ethoxycyclohex-2-en-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:

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

Procedure: 3-Ethoxycyclohex-2-enone (25 g) was dissolved in diethyl ether (500 mL), and tetraisopropoxytitanium (55 mL) was added, followed by the addition of ethyl magnesium bromide (3.0M in diethyl ether, 180 mL) over 30 minutes. The reaction was stirred at room temperature for another two hours, and quenched by the careful addition of water (250 mL). The mixture was filtered through diatomaceous earth, and rinsed with diethyl ether. The filtrate was transferred to a separatory funnel, the aqueous layer was drawn off, and p-toluenesulfonic acid monohydrate (2 g) was added to the organic layer, which was stirred at room temperature for two days. The reaction mixture was washed with saturated aqueous NaHCO3 and brine, then dried over Na2SO4. The mixture was filtered, and concentrated and chromatography on silica gel using 93/7 hexanes/ethyl acetate provided the title compound. quenched by the careful addition of water (250 mL) The mixture was filtered through diatomaceous earth rinsed with diethyl ether The filtrate was transferred to a separatory funnel p-toluenesulfonic acid monohydrate (2 g) was added to the organic layer, which was stirred at room temperature for two days The reaction mixture was washed with saturated aqueous NaHCO3 and brine dried over Na2SO4 The mixture was filtered 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 0.5N ethynylmagnesium bromide in tetrahydrofuran (100 mL) was added under N2 and stirring 3-ethoxy-2-cyclohexen-1-one (3.75 g, 26.8 mmol) in tetrahydrofuran (12.5 mL). The mixture was stirred at RT for 20 h when it was acidified with 1N HCl (200 mL). After stirring for 15 min the acidic phase was extracted with dichloromethane (5×50 mL). The combined organic extracts were washed with water (2×50 mL) and dried (MgSO4). Evaporation of the solvent gave an oil that was purified by column chromatography (silica, ethyl acetate/hexane 1:9) to yield a yellow oil, 2.71 g, 22.6 mmol, 84%). Analysis were in agreement with literature data. After stirring for 15 min the acidic phase was extracted with dichloromethane (5×50 mL) The combined organic extracts were washed with water (2×50 mL) dried (MgSO4) Evaporation of the solvent gave an oil that was purified by column chromatography (silica, ethyl acetate/hexane 1:9) to yield a yellow oil, 2.71 g, 22.6 mmol, 84%)

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

Procedure: The title compound (D12) was prepared from 3-ethoxy-2-cyclohexen-1-one and ethyl iodide using a procedure similar to that described in Description 11. Product was used in the preparation of D14 without further purification. Product was used in the preparation of D14 without further purification

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

Procedure: To a stirred solution of lithium diisopropylamide mono (tetrahydrofuran) (100 ml, 150 mM, 1.5M solution) in dry tetrahydrofuran (100 ml) under an atmosphere of nitrogen and at -78° C. was added dropwise 3-ethoxy-2-cyclohexen-1-one (21.0 g, 150 mM) dissolved in tetrahydrofuran (70 ml) over a period of 15 min. After an additional 45 min, methyl iodide (21.29 g, 150 mM) dissolved in dry tetrahydrofuran (10 ml) was added dropwise over a period of 5 min. After a further 15 min the cooling bath was removed and the whole stirred at room temperature for 1 h. Water was then added and the enol ether intermediate recovered into ether, washed (brine), dried (Na2SO4) and evaporated to dryness. The oil thus obtained was dissolved in ethanol (100 ml) and 5N hydrochloric acid (228 ml) added. The whole was stirred at room temperature for 45 min. Water (800 ml) was added, the aqueous phase made basic to pH 8-9 (NaOH) and extracted with ethyl acetate. The aqueous phase was re-acidified (HCl) and the product extracted into ethyl acetate. The organic phase was washed with brine, dried (Na2SO4) and evaporated to give the title compound (D11) (17.6 g) (92%) as an oil. Product could be used directly in the preparation of intermediate D13 without further purification. was added dropwise over a period of 5 min After a further 15 min the cooling bath was removed Water was then added the enol ether intermediate recovered into ether washed (brine) dried (Na2SO4) evaporated to dryness The oil thus obtained The whole was stirred at room temperature for 45 min extracted with ethyl acetate the product extracted into ethyl acetate The organic phase was washed with brine dried (Na2SO4) evaporated

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

Procedure: A solution of 25 g. (0.178 mole) of 3-ethoxy-2-cyclohexen-1-one in 25 ml. of tetrahydrofuran is added dropwise (30 min.) to a -78° C. solution of 0.196 mole of lithium diisopropylamide (from 27.4 ml., 0.196 mole, of diisopropylamine and 85 ml., 0.187 mole, of 2.2 M n-butyl lithium in hexane) in 125 ml. of tetrahydrofuran. The reaction is stirred 30 minutes longer and then 65 ml. (0.374 mole) of hexamethylphosphoramide is added followed by 38.9 ml. (0.383 mole) of 4-bromo-1-butene. The reaction is then allowed to warm to room temperature, stirred 1.5 hours and quenched by addition of 5 ml. (0.277 mole) of water. Most of the solvent is removed under reduced pressure and the residue diluted with one liter ice water and 500 ml. ether. The ether extract is washed with two 300 ml. portions of water, dried over magnesium sulfate and evaporated. Distillation of the crude oil yields 10.1 g. (29%) of the title product. stirred 1.5 hours quenched by addition of 5 ml Most of the solvent is removed under reduced pressure the residue diluted with one liter ice water and 500 ml The ether extract is washed with two 300 ml portions of water, dried over magnesium sulfate evaporated Distillation of the crude oil yields 10.1 g

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

Procedure: A solution of 25 g. (0.178 mole) of 3-ethoxy-2-cyclohexen-1-one in 25 ml. of tetrahydrofuran is added dropwise (30 min.) to a -78° C. solution of 0.196 mole of lithium diisopropylamide (from 27.4 ml., 0.196 mole, of diisopropylamine and 85 ml., 0.187 mole, of 2.2 M n-butyl lithium in hexane) in 125 ml. of tetrahydrofuran. The reaction is stirred 30 minutes longer and then 65 ml. (0.374 mole) of hexamethylphosphoramide is added followed by 38.9 ml. (0.383 mole) of 4-bromo-1-butene. The reaction is then allowed to warm to room temperature, stirred 1.5 hours and quenched by addition of 5 ml. (0.277 mole) of water. Most of the solvent is removed under reduced pressure and the residue diluted with one liter ice water and 500 ml. ether. The ether extract is washed with two 300 ml. portions of water, dried over magnesium sulfate and evaporated. Distillation of the crude oil yields 10.1 g. (29%) of the title product. stirred 1.5 hours quenched by addition of 5 ml Most of the solvent is removed under reduced pressure the residue diluted with one liter ice water and 500 ml The ether extract is washed with two 300 ml portions of water, dried over magnesium sulfate evaporated Distillation of the crude oil yields 10.1 g

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

Procedure: A solution of 3.89 g. (10 mmoles) of 2-(3-benzyloxy-4-bromophenyl)-2-methyloctane in 10 ml. of tetrahydrofuran was slowly added to 360 mg. (14.4 mmoles) of 70-80 mesh magnesium metal. The resulting mixture was refluxed for 30 minutes and then cooled to 0° C. To this solution was slowly added a solution of 1.40 g. (10 mmoles) of 3-ethoxy-2-cyclohexen-1-one in 3 ml. of tetrahydrofuran. The reaction mixture was stirred for 30 minutes at 0° C. and then quenched by the addition of 20 ml. of 1 N sulfuric acid and heating on the steam bath for 30 minutes. It was then cooled and added to 200 ml. of ether-200 ml. of water. The organic extract was washed successively with 200 ml. of saturated sodium bicarbonate and 200 ml. of saturated sodium chloride, dried over magnesium sulfate and evaporated to an oil. The crude product was purified via column chromatography on 170 g. of silica gel eluted with 1:1 ether:pentane to yield 2.5 g. (54%) of the title compound as an oil. The resulting mixture was refluxed for 30 minutes To this solution was slowly added a solution of 1.40 g quenched by the addition of 20 ml of 1 N sulfuric acid and heating on the steam bath for 30 minutes It was then cooled added to 200 ml The organic extract was washed successively with 200 ml of saturated sodium chloride, dried over magnesium sulfate evaporated to an oil The crude product was purified via column chromatography on 170 g of silica gel eluted with 1:1 ether pentane to yield 2.5 g