methyl 7-(3-hydroxy-5-oxocyclopenten-1-yl)heptanoate

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: 4-Hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone (24 g) was dissolved in chloroform (200 ml), followed by addition of acetyl chloride (7.9 g) thereto. Triethylamine [10.1 g) was dropwise added thereto while stirring at 0° to 10° C. After completion of the addition, stirring was continued at 25° C. for 8 hours. The reaction mixture was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4-acetoxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone (27.6 g). Yield, 98%. After completion of the addition stirring The reaction mixture was washed with water dried over anhydrous magnesium sulfate concentrated under reduced pressure

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

Procedure: 4-Hydroxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone (24 g) was dissolved in chloroform (200 ml), followed by addition of acetyl chloride (7.9 g) thereto. Triethylamine [10.1 g) was dropwise added thereto while stirring at 0° to 10° C. After completion of the addition, stirring was continued at 25° C. for 8 hours. The reaction mixture was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4-acetoxy-2-(6-methoxycarbonylhexyl)-2-cyclopentenone (27.6 g). Yield, 98%. After completion of the addition stirring The reaction mixture was washed with water dried over anhydrous magnesium sulfate concentrated under reduced pressure

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

Procedure: A solution of 1.47 parts of 3(RS)-(tetrahydropyran-2-yl)oxy-1-octyne in 7.1 parts of ether is treated at -40° with 2.6 parts by volume of a 2.3 M butyl lithium in hexane solution. The reaction mixture is stirred at room temperature for 1 hour, then cooled to -40°. 0.267 Part of aluminum trichloride is added and the mixture is stirred at room temperature for 2 hours. After that time, 0.240 part of methyl 3(RS)-hydroxy-5-oxocyclopent-1-eneheptanoate, dissolved in ether, is added and the resulting mixture is stirred at room temperature for about 16 hours. The reaction mixture then is poured into a mixture of 35.5 parts of ether and 20 parts by volume of an aqueous 0.5 N hydrochloric acid solution. The ethereal layer is separated, washed with water, dried over anhydrous sodium sulfate and stripped of solvent. The remaining material is chromatographed on silica gel with 20% ethyl acetate in benzene as eluent to yield, as a stereoisomeric mixture, methyl 3(RS)-hydroxy-2-(3(RS)-[tetrahydropyran-2-yl]oxy-1-octynyl)-5-oxocyclopentane-heptanoate. cooled to -40° the mixture is stirred at room temperature for 2 hours is added the resulting mixture is stirred at room temperature for about 16 hours The ethereal layer is separated washed with water dried over anhydrous sodium sulfate The remaining material is chromatographed on silica gel with 20% ethyl acetate in benzene as eluent

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

Procedure: A mixture consisting of 0.240 part of methyl 3(RS)-hydroxy-5-oxocyclopent-1-eneheptanoate, 0.200 part of 2(S)- aminoxyisocaproic acid and 4 parts of methanol is treated with 0.5 part of pyridine. That mixture is allowed to stand at room temperature for about 16 hours and then is poured into 45 parts of ethyl acetate and 20 parts by volume of 0.5 N hydrochloric acid. The ethyl acetate layer is separated, washed with water and dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is chromatographed on silica gel using 1% ethyl acetate in chloroform as eluent to afford successive fractions of methyl 3(R)-hydroxy-5[(1-carboxyisoamyl)oxyimino]cyclopent-1-eneheptanoate, melting at about 62°-63° and methyl 3(S)-hydroxy-5-[(1-carboxyisoamyl)oxyimino]cyclopent-1-eneheptanoate. The ethyl acetate layer is separated washed with water dried over anhydrous sodium sulfate The solvent is removed by evaporation under reduced pressure the residue is chromatographed on silica gel using 1% ethyl acetate in chloroform as eluent

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

Procedure: A mixture consisting of 0.240 part of methyl 3(RS)-hydroxy-5-oxocyclopent-1-eneheptanoate, 0.200 part of 2(S)- aminoxyisocaproic acid and 4 parts of methanol is treated with 0.5 part of pyridine. That mixture is allowed to stand at room temperature for about 16 hours and then is poured into 45 parts of ethyl acetate and 20 parts by volume of 0.5 N hydrochloric acid. The ethyl acetate layer is separated, washed with water and dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is chromatographed on silica gel using 1% ethyl acetate in chloroform as eluent to afford successive fractions of methyl 3(R)-hydroxy-5[(1-carboxyisoamyl)oxyimino]cyclopent-1-eneheptanoate, melting at about 62°-63° and methyl 3(S)-hydroxy-5-[(1-carboxyisoamyl)oxyimino]cyclopent-1-eneheptanoate. The ethyl acetate layer is separated washed with water dried over anhydrous sodium sulfate The solvent is removed by evaporation under reduced pressure the residue is chromatographed on silica gel using 1% ethyl acetate in chloroform as eluent

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

Procedure: To 1.0 part of 3(RS)-hydroxy-5-oxocyclopent-1-eneheptanoic acid dissolved in methanol is added dropwise a 5% ethereal diazomethane solution until a slight excess of diazomethane is present. That excess is detected when the solution exhibits a persistent yellow color. The solution then is evaporated to dryness under a nitrogen atmosphere to yield methyl 3(RS)-hydroxy-5-oxocyclopent-1-eneheptanoate. The solution then is evaporated to dryness under a nitrogen atmosphere

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

Procedure: The 3-hydroxy-3-alkylated acetylenic compounds of this invention are prepared by employing the appropriately alkylated alkynyl boron, alkynyl gallium or alkynyl aluminum reactant. For example, treatment of methyl 3-hydroxy-5-oxocyclopent-1-eneheptanoate with tri(3methyl-3-[tetrahydropyran-2-yl]oxy-1-octynyl) aluminum, gallium or boron affords the epimeric methyl 3-hydroxy-2-(3-methyl-3-[tetrahydropyran-2-yl]oxy-1-octynyl)-5-oxocyclopentaneheptanoate. Typically, that compound may be hydrolyzed with a hydrolyzing agent such as hydrolytic acid, e.g. aqueous acetic acid, to yield the instant methyl 3-hydroxy-2-(3-hydroxy-3-methyl-1-octynyl)-5-oxocyclopentaneheptanoate.

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

Procedure: The 3-hydroxy-3-alkylated acetylenic compounds of this invention are prepared by employing the appropriately alkylated alkynyl boron, alkynyl gallium or alkynyl aluminum reactant. For example, treatment of methyl 3-hydroxy-5-oxocyclopent-1-eneheptanoate with tri(3methyl-3-[tetrahydropyran-2-yl]oxy-1-octynyl) aluminum, gallium or boron affords the epimeric methyl 3-hydroxy-2-(3-methyl-3-[tetrahydropyran-2-yl]oxy-1-octynyl)-5-oxocyclopentaneheptanoate. Typically, that compound may be hydrolyzed with a hydrolyzing agent such as hydrolytic acid, e.g. aqueous acetic acid, to yield the instant methyl 3-hydroxy-2-(3-hydroxy-3-methyl-1-octynyl)-5-oxocyclopentaneheptanoate.

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

Procedure: A mixture of 0.240 part of methyl 3-hydroxy-5-oxocyclopent-1-eneheptanoate, 10 parts by volume of 0.1 N sodium hydroxide and 7.9 parts of methanol is allowed to stand at room temperature for 16 hours, then diluted with water and extracted with ethyl acetate. The aqueous layer is acidified with 1 N hydrochloric acid and then extracted with ethyl acetate. The ethyl acetate extract is washed with water, dried over anhydrous sodium sulfate and stripped of solvent under reduced pressure. Chromatography of the crude product on silica gel with 50% ethyl acetate-benzene affords 3-hydroxy-5-oxocyclopent-1-eneheptanoic acid, melting at about 47°-48.5°. That compound is characterized further by absorption in the ultravoilet spectrum at about 222 millimicrons with a molecular extinction coefficient of about 7700 and a maximum in the nuclear magnetic resonance spectrum at about 87.2 ppm. extracted with ethyl acetate extracted with ethyl acetate The ethyl acetate extract is washed with water dried over anhydrous sodium sulfate

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

Procedure: 10 Parts of sulfuric acid is treated with 9 parts of 20% fuming sulfuric acid and allowed to stand at room temperature for 10 minutes. 1.25 Parts by volume of that solution then is added dropwise to 28.5 parts by volume of 1M lithium aluminum hydride in tetrahydrofuran. After the addition is complete, the temperature is maintained at -60° for 15 minutes and then allowed to rise to room temperature. The aluminum hydride solution so obtained is cooled to -60° and added rapidly to a solution of 6.92 parts of methyl 2-methoxy-4-hydroxy-5-oxocyclopent-1-eneheptanoate dissolved in 310 parts of redistilled tetrahydrofuran which is cooled to -40°. The temperature is lowered to -70° after the addition is complete and the reaction mixture is stirred at that temperature for 33/4 hours. Then 7.9 parts of methanol in 17.8 parts of tetrahydrofuran is added slowly and the temperature is allowed to rise to -20° at which time 120 parts by volume of a 1 N aqueous hydrochloric acid solution is added. The mixture is allowed to stand at about 4° for 16 hours and then the solvent is removed under reduced pressure. The aqueous residue which remains is diluted with ethyl acetate and the organic and aqueous layers separated. The organic layer is washed with water, potassium bicarbonate and water. Then it is dried over anhydrous sodium sulfate and the solvent is removed under reduced pressure to afford methyl 3-hydroxy-5-oxocyclopent-1-eneheptanoate. is cooled to -60° is cooled to -40° is lowered to -70° after the addition is added to stand at about 4° for 16 hours the solvent is removed under reduced pressure The aqueous residue which remains is diluted with ethyl acetate the organic and aqueous layers separated The organic layer is washed with water, potassium bicarbonate and water Then it is dried over anhydrous sodium sulfate the solvent is removed under reduced pressure