7-(oxan-2-yloxy)heptanal

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)heptanal (22 g) and 1-morpholinocyclopentene (21.4 g), i.e. the morpholine enamine of cyclopentanone, in benzene (25 ml) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml) and then, dropwise, 18% hydrochloric acid (28 ml) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml) and butanol (300 ml) were added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)cyclopent-2-enone (11.7 g), b.p. 125°-170° C./0.15 mm Hg, nD25 =1.490, λmax 228 mμ (ethanol). under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml) and then, dropwise, 18% hydrochloric acid (28 ml) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml) and butanol (300 ml) were added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)-heptanal (22 g.) and 1-morpholinocyclopentene, i.e. the morpholine enamine of cyclopentanone, (21.4 g.) in benzene (25 ml.) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml.) was added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added, and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)-cyclopent-2-enone (11.7 g.), b.p. 125°-170° C./0.15 mm.Hg, nD25 = 1.490, λmax 228mμ (ethanol). was heated under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml.) was added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminium hydride (19.4 g.) in dry benzene (50 ml.) was added dropwise at 10° C. to a stirred solution of 7-(2-tetrahydropyranyloxy)heptanenitrile (20.6 g.) in dry diethyl ether (200 ml.). The solution was stirred at 10° C. for 30 minutes and was then added to 2N aqueous sulphuric acid (300 ml.) at 0° C. The mixture was heated at 30° C. for 30 minutes, and then saturated with sodium chloride and the layers were separated. The aqueous layer was extracted with diethyl ether and the combined organic layers were washed with aqueous sodium bicarbonate, and then aqueous sodium chloride, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 7-(2-tetrahydropyranyloxy)heptanal (12.7 g.), b.p. 78°-106° C./0.1 mm.Hg, nD25 1.456. The mixture was heated at 30° C. for 30 minutes saturated with sodium chloride and the layers were separated The aqueous layer was extracted with diethyl ether the combined organic layers were washed with aqueous sodium bicarbonate aqueous sodium chloride, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)heptanal (22 g.) and 1-morpholinocyclopentene, i.e. the morpholine enamine of cyclopentanone, (21.4 g.) in benzene (25 ml.) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml.) and butanol (300 ml.) were added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added, and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)cyclopent-2-en-1-one (11.7 g.), b.p. 125°-170° C/0.15 mm.Hg, nD25 1.490, μmax 228mμ (ethanol). was heated under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml.) and butanol (300 ml.) were added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

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

Procedure: A solution of 20.37 g of 7-(tetrahydropyran-2-yloxy)-1-heptanol in 200 ml of methylene chloride was added, whilst ice-cooling, to a mixture of 40.60 g of pyridinium chlorochromate, 3.86 g of sodium acetate and 200 ml of methylene chloride. The resulting mixture was stirred at 0° C. for 1 hour and then at room temperature for 3 hours, after which was diluted with 1.5 liter of diethyl ether and passed through a column containing 250 g of silica gel. The eluate was concentrated by evaporation under reduced pressure, and the residue was subjected to column chromatography through 400 g of silica gel. 14.11 g of 7-(tetrahydropyran-2-yloxy)heptanal were obtained, as a colorless oil, from those fractions eluted with mixtures of hexane and ethyl acetate ranging from 40:1 to 9:1 by volume. at room temperature for 3 hours containing 250 g of silica gel The eluate was concentrated by evaporation under reduced pressure

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminium hydride (19.4 g.) in dry benzene (50 ml.) was added dropwise at 10° C. to a stirred solution of 7-(2-tetrahydropyranyloxy)heptanenitrile (20.6 g.) in dry diethyl ether (200 ml.). The solution was stirred at 10° C. for 30 minutes and was then added to 2 N aqueous sulphuric acid (300 ml.) at 0° C. The mixture was heated at 30° C. for 30 minutes, and then saturated with sodium chloride and the layers were separated. The aqueous layer was extracted with diethyl ether and the combined organic layers were washed with aqueous sodium bicarbonate, and then aqueous sodium chloride, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 7-(2-tetrahydropyranyloxy)-heptanal (12.7 g.), b.p. 78°-106° C./0.1 mm.Hg, nD25 1.456. The mixture was heated at 30° C. for 30 minutes saturated with sodium chloride and the layers were separated The aqueous layer was extracted with diethyl ether the combined organic layers were washed with aqueous sodium bicarbonate aqueous sodium chloride, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminium hydride (19.4 g.) in dry benzene (50 ml.) was added dropwise at 10° C. to a stirred solution of 7-(2-tetrahydropyranyloxy)heptanenitrile (20.6 g.) in dry diethyl ether (200 ml.). The solution was stirred at 10° C. for 30 minutes and was then added to 2 N aqueous sulphuric acid (300 ml.) at 0° C. The mixture was heated at 30° C. for 30 minutes, and then saturated with sodium chloride and the layers were separated. The aqueous layer was extracted with diethyl ether and the combined organic layers were washed with aqueous sodium bicarbonate, and then aqueous sodium chloride, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 7-(2-tetrahydropyranyloxy)-heptanal (12.7 g.), b.p. 78°-106° C./0.1 mm.Hg, nD25 1.456. The mixture was heated at 30° C. for 30 minutes saturated with sodium chloride and the layers were separated The aqueous layer was extracted with diethyl ether the combined organic layers were washed with aqueous sodium bicarbonate aqueous sodium chloride, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)heptanal (22 g.) and 1-morpholinocyclopentene, i.e. the morpholine enamine of cyclopentanone, (21.4 g.) in benzene (25 ml.) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml.) and butanol (300 ml.) were added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added, and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)cyclopent-2-en-1-one (11.7 g.), b.p. 125°-170° C./0.15 mm.Hg, nD25 1.490, λmax 228 mμ (ethanol). was heated under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml.) and butanol (300 ml.) were added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)heptanal (22 g.) and 1-morpholinocyclopentene, i.e. the morpholine enamine of cyclopentanone, (21.4 g.) in benzene (25 ml.) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml.) and butanol (300 ml.) were added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added, and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)cyclopent-2-en-1-one (11.7 g.), b.p. 125°-170° C./0.15 mm.Hg, nD25 1.490, λmax 228 mμ (ethanol). was heated under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml.) and butanol (300 ml.) were added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)heptanal (22 g.) and 1-morpholinocyclopentene, i.e. the morpholine enamine of cyclopentanone, (21.4 g.) in benzene (25 ml.) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml.) was added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added, and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)cyclopent-2-enone (11.7 g.), b.p. 125°- 170° C./0.15 mm.Hg, nD25 = 1.490, Λmax 228mμ (ethanol). was heated under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml.) was added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)heptanal (22 g) and 1-morpholinocyclopentene (21.4 g), i.e. the morpholine enamine of cyclopentanone, in benzene (25 ml) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml) and then, dropwise, 18% hydrochloric acid (28 ml) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml) and butanol (300 ml) were added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)cyclopent-2-enone (11.7 g), b.p. 125°-170° C./0.15 mm Hg, nD25 =1.490, λmax 228 mμ (ethanol). under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml) and then, dropwise, 18% hydrochloric acid (28 ml) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml) and butanol (300 ml) were added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(2-tetrahydropyranyloxy)-heptanal (22 g.) and 1-morpholinocyclopentene, i.e. the morpholine enamine of cyclopentanone, (21.4 g.) in benzene (25 ml.) was heated under reflux for 12 hours under nitrogen, and the water liberated was continuously removed with a Dean and Stark head. Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added and the mixture was stirred for 2 hours. The organic layer was separated and evaporated. Concentrated hydrochloric acid (72 ml.) was added to the residue. The mixture was heated at 100° C. for 1 hour, and then the solution was concentrated to give an oil. Diethyl ether was added, and the ether solution was washed with aqueous sodium bicarbonate and then water, and dried over sodium sulphate. The solvent was evaporated and the residue was distilled under reduced pressure to give 2-(7-hydroxyheptyl)-cyclopent-2-enone (11.7 g.), b.p. 125°-170° C./0.15 mm.Hg, nD25 = 1.490, λmax 228mμ (ethanol). was heated under reflux for 12 hours under nitrogen the water liberated was continuously removed with a Dean and Stark head Benzene (10 ml.) and then, dropwise, 18% hydrochloric acid (28 ml.) were added The organic layer was separated evaporated Concentrated hydrochloric acid (72 ml.) was added to the residue the solution was concentrated to give an oil the ether solution was washed with aqueous sodium bicarbonate water, and dried over sodium sulphate The solvent was evaporated the residue was distilled under reduced pressure