(2E)-hepta-2,6-dienoic acid

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

Procedure: Oxalyl chloride (10 mL) was added dropwise to a toluene solution (60 mL) of (2E)-hepta-2,6-dienoic acid (3.27 g, 25.9 mmol) under ice cooling. The mixture was stirred for 20 minutes, then removed from the ice water bath, and gradually heated to room temperature. After stirring for 50 minutes, the reaction solution was stirred for 1 hour under heating to reflux. The solution was allowed to cool, and the solvent was then distilled off under reduced pressure. To the residue, toluene was further added, and the solvent was then distilled off again under reduced pressure. The residue was dissolved in toluene (20 mL), and this solution was added dropwise over 1 hour to a toluene solution (20 mL) of triethylamine (9.19 g, 91 mmol) heated in advance to 90° C. After completion of the dropwise addition, the mixture was further heated with stirring for 2 hours. The reaction solution was cooled, then diluted with saturated saline and water, and filtered through Celite. The filtrate was separated into organic and aqueous layers. The organic layer was then washed with 1 N hydrochloric acid, then dried over magnesium sulfate, and filtered. This filtrate was added to a reaction solution prepared in advance from a dimethoxyethane solution (20 mL) of tert-butyl dimethoxyphosphorylacetate (5.98 g, 25.9 mmol) and sodium hydride (>65% oil, 986.7 mg, 25.9 mmol), and the mixture was stirred for 1.5 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride, saturated saline, and water were added in this order, and the reaction solution was subjected to extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture). removed from the ice water bath After stirring for 50 minutes the reaction solution was stirred for 1 hour under heating to reflux to cool the solvent was then distilled off under reduced pressure To the residue, toluene was further added the solvent was then distilled off again under reduced pressure The residue was dissolved in toluene (20 mL) heated in advance to 90° C After completion of the dropwise addition the mixture was further heated with stirring for 2 hours The reaction solution was cooled filtered through Celite The filtrate was separated into organic and aqueous layers The organic layer was then washed with 1 N hydrochloric acid dried over magnesium sulfate filtered This filtrate was added to a reaction solution the mixture was stirred for 1.5 hours the reaction solution was subjected to extraction with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture)

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

Procedure: Oxalyl chloride (10 mL) was added dropwise to a toluene solution (60 mL) of (2E)-hepta-2,6-dienoic acid (3.27 g, 25.9 mmol) under ice cooling. The mixture was stirred for 20 minutes, then removed from the ice water bath, and gradually heated to room temperature. After stirring for 50 minutes, the reaction solution was stirred for 1 hour under heating to reflux. The solution was allowed to cool, and the solvent was then distilled off under reduced pressure. To the residue, toluene was further added, and the solvent was then distilled off again under reduced pressure. The residue was dissolved in toluene (20 mL), and this solution was added dropwise over 1 hour to a toluene solution (20 mL) of triethylamine (9.19 g, 91 mmol) heated in advance to 90° C. After completion of the dropwise addition, the mixture was further heated with stirring for 2 hours. The reaction solution was cooled, then diluted with saturated saline and water, and filtered through Celite. The filtrate was separated into organic and aqueous layers. The organic layer was then washed with 1 N hydrochloric acid, then dried over magnesium sulfate, and filtered. This filtrate was added to a reaction solution prepared in advance from a dimethoxyethane solution (20 mL) of tert-butyl dimethoxyphosphorylacetate (5.98 g, 25.9 mmol) and sodium hydride (>65% oil, 986.7 mg, 25.9 mmol), and the mixture was stirred for 1.5 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride, saturated saline, and water were added in this order, and the reaction solution was subjected to extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture). removed from the ice water bath After stirring for 50 minutes the reaction solution was stirred for 1 hour under heating to reflux to cool the solvent was then distilled off under reduced pressure To the residue, toluene was further added the solvent was then distilled off again under reduced pressure The residue was dissolved in toluene (20 mL) heated in advance to 90° C After completion of the dropwise addition the mixture was further heated with stirring for 2 hours The reaction solution was cooled filtered through Celite The filtrate was separated into organic and aqueous layers The organic layer was then washed with 1 N hydrochloric acid dried over magnesium sulfate filtered This filtrate was added to a reaction solution the mixture was stirred for 1.5 hours the reaction solution was subjected to extraction with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Pentenal (4.45 g, 51.4 mmol) and malonic acid (6.41 g, 61.6 mmol) were dissolved in pyridine (9.9 mL). To the solution, piperidine (1.9 mL) was added, and the mixture was then stirred at 90° C. for 5 hours. The mixture was allowed to cool and then made acidic by the addition of 2 N hydrochloric acid, followed by extraction with diethyl ether. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the filtrate was then concentrated under reduced pressure. The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%). to cool followed by extraction with diethyl ether The organic layer was washed with saturated saline dried over anhydrous magnesium sulfate the filtrate was then concentrated under reduced pressure The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%)

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

Procedure: Oxalyl chloride (10 mL) was added dropwise to a solution of (2E)-hepta-2,6-dienoic acid (3.27 g, 25.9 mmol) in toluene (60 mL) under ice cooling. The mixture was stirred for 20 minutes, then removed from the ice water bath, and gradually heated to room temperature. After stirring for 50 minutes, the reaction solution was stirred for 1 hour under heating to reflux. The solution was allowed to cool, and the solvent was then distilled off under reduced pressure. To the residue, toluene was further added, and the solvent was then distilled off again under reduced pressure. The residue was dissolved in toluene (20 mL), and this solution was added dropwise over 1 hour to a solution of triethylamine (9.19 g, 91 mmol) in toluene (20 mL) heated in advance to 90° C. After the completion of the dropwise addition, the mixture was further heated with stirring for 2 hours. The reaction solution was cooled, then diluted with saturated saline and water, and filtered through Celite. The filtrate was separated into organic and aqueous layers. The organic layer was then washed with 1 N hydrochloric acid, then dried over magnesium sulfate, and filtered. The filtrate was added to a reaction solution prepared in advance from a solution of tert-butyl dimethoxyphosphorylacetate (5.98 g, 25.9 mmol) in dimethoxyethane (20 mL) and sodium hydride (>65% oil, 986.7 mg, 25.9 mmol), and the mixture was stirred for 1.5 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride, saturated saline, and water were added in this order, and the reaction solution was subjected to extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture). removed from the ice water bath After stirring for 50 minutes the reaction solution was stirred for 1 hour under heating to reflux to cool the solvent was then distilled off under reduced pressure To the residue, toluene was further added the solvent was then distilled off again under reduced pressure The residue was dissolved in toluene (20 mL) heated in advance to 90° C After the completion of the dropwise addition the mixture was further heated with stirring for 2 hours The reaction solution was cooled filtered through Celite The filtrate was separated into organic and aqueous layers The organic layer was then washed with 1 N hydrochloric acid dried over magnesium sulfate filtered The filtrate was added to a reaction solution the mixture was stirred for 1.5 hours the reaction solution was subjected to extraction with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Pentenal (4.45 g, 51.4 mmol) and malonic acid (6.41 g, 61.6 mmol) were dissolved in pyridine (9.9 mL). To the solution, piperidine (1.9 mL) was added, and the mixture was then stirred at 90° C. for 5 hours. The mixture was allowed to cool and then made acidic by the addition of 2 N hydrochloric acid, followed by extraction with diethyl ether. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the filtrate was then concentrated under reduced pressure. The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%). to cool followed by extraction with diethyl ether The organic layer was washed with saturated saline dried over anhydrous magnesium sulfate the filtrate was then concentrated under reduced pressure The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%)

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

Procedure: Oxalyl chloride (10 mL) was added dropwise to a toluene solution (60 mL) of (2E)-hepta-2,6-dienoic acid (3.27 g, 25.9 mmol) under ice cooling. The mixture was stirred for 20 minutes, then removed from the ice water bath, and gradually heated to room temperature. After stirring for 50 minutes, the reaction solution was stirred for 1 hour under heating to reflux. The solution was allowed to cool, and the solvent was then distilled off under reduced pressure. To the residue, toluene was further added, and the solvent was then distilled off again under reduced pressure. The residue was dissolved in toluene (20 mL), and this solution was added dropwise over 1 hour to a toluene solution (20 mL) of triethylamine (9.19 g, 91 mmol) heated in advance to 90° C. After completion of the dropwise addition, the mixture was further heated with stirring for 2 hours. The reaction solution was cooled, then diluted with saturated saline and water, and filtered through Celite. The filtrate was separated into organic and aqueous layers. The organic layer was then washed with 1 N hydrochloric acid, then dried over magnesium sulfate, and filtered. This filtrate was added to a reaction solution prepared in advance from a dimethoxyethane solution (20 mL) of tert-butyl dimethoxyphosphorylacetate (5.98 g, 25.9 mmol) and sodium hydride (>65% oil, 986.7 mg, 25.9 mmol), and the mixture was stirred for 1.5 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride, saturated saline, and water were added in this order, and the reaction solution was subjected to extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture). removed from the ice water bath After stirring for 50 minutes the reaction solution was stirred for 1 hour under heating to reflux to cool the solvent was then distilled off under reduced pressure To the residue, toluene was further added the solvent was then distilled off again under reduced pressure The residue was dissolved in toluene (20 mL) heated in advance to 90° C After completion of the dropwise addition the mixture was further heated with stirring for 2 hours The reaction solution was cooled filtered through Celite The filtrate was separated into organic and aqueous layers The organic layer was then washed with 1 N hydrochloric acid dried over magnesium sulfate filtered This filtrate was added to a reaction solution the mixture was stirred for 1.5 hours the reaction solution was subjected to extraction with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.73 g, 32%, E/Z mixture)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Pentenal (4.45 g, 51.4 mmol) and malonic acid (6.41 g, 61.6 mmol) were dissolved in pyridine (9.9 mL). To the solution, piperidine (1.9 mL) was added, and the mixture was then stirred at 90° C. for 5 hours. The mixture was allowed to cool and then made acidic by the addition of 2 N hydrochloric acid, followed by extraction with diethyl ether. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the filtrate was then concentrated under reduced pressure. The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%). to cool followed by extraction with diethyl ether The organic layer was washed with saturated saline dried over anhydrous magnesium sulfate the filtrate was then concentrated under reduced pressure The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%)