1-bromooct-2-yne

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: A solution of ethyl magnesium bromide in tetrahydrofuran (47 mL, 1.17 M) was treated dropwise with a solution of (E)-4-methyl-3,5-dioxa-7-decen-9-yne (7.7 g) in tetrahydrofuran (10 mL). After complete addition, the mixture was heated at 60° for 45 min, cooled to room temperature, treated with anhydrous cuprous chloride (0.35 g, dried at 145° at 0.05 mmHg for 16 hours) and stirred for 10 min. The 1-bromo-2-octyne (7.23 g) in tetrahydrofuran (10 mL) was added dropwise to the above mixture (mild exothermic reaction) and after complete addition the resulting mixture was heated for 45 min at 60° C. After this time, the contents were cooled to room temperature, poured onto saturated aqueous ammonium chloride solution and extracted with ether. The combined ether extracts were washed with brine, dried (MgSO4) and concentrated. The residue was purified by liquid chromatography (two columns, 3% by volume ethyl acetate in 97% by volume hexane) to yield the product (E)-4-methyl-3,5-dioxa-7-octadecen-9,12-diyne After complete addition the mixture was heated at 60° for 45 min after complete addition the resulting mixture was heated for 45 min at 60° C After this time, the contents were cooled to room temperature extracted with ether The combined ether extracts were washed with brine dried (MgSO4) concentrated The residue was purified by liquid chromatography (two columns, 3% by volume ethyl acetate in 97% by volume hexane)

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

Procedure: A solution of 2-octyne-1-ol (37.8 g) in ether (150 mL) containing pyridine (3 ml) was cooled to -35° and treated with a solution of phosphorous tribromide (28.9 g) over 45 min. The mixture was then stirred at -30° for 2 hours, 3 hours at room temperature and 1/2 hour at 40°. The reaction mixture was then cooled to room temperature, poured onto ice and extracted with ether. The combined ether extracts were washed with aqueous NaHCO3 solution, brine and dried (MgSO4). Removal of the solvents and distillation of the residue yielded 1-bromo-2-octyne (40.9 g), bp, 106°-110° (25 mmHg). was cooled to -35° The reaction mixture was then cooled to room temperature poured onto ice extracted with ether The combined ether extracts were washed with aqueous NaHCO3 solution, brine dried (MgSO4) Removal of the solvents and distillation of the residue

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

Procedure: Under argon atmosphere, anhydrous pyridine (0.4 ml, 4.9 mmol) was added to a solution of 2-octyne-1-ol (9.4658 g, 75.0 mmol) in anhydrous ether (50 ml). To the mixture was added dropwise phosphorus tribromide (2.35 ml, 25.0 mmol) at -30° to -35° C. and the mixture was stirred at the same temperature for one hour and then stirred for one hour at room temperature under argon atmosphere. To the resulting mixture was added brine (100 ml), and the mixture was then extracted with ether (50 ml×4). The combined ether layers were washed with an aqueous saturated solution of sodium bicarbonate (150 ml), with water (150 ml) and with brine (150 ml), dried over anhydrous sodium sulfate (40 g), and concentrated. Distillation of the residue gave a colorless oily product of 1-bromo-2-octyne (9.1493 g, 65%, B.p.: 53°-58° C./0.39 mmHg). The product was assigned the structure by the following data. stirred for one hour at room temperature under argon atmosphere the mixture was then extracted with ether (50 ml×4) The combined ether layers were washed with an aqueous saturated solution of sodium bicarbonate (150 ml), with water (150 ml) and with brine (150 ml) dried over anhydrous sodium sulfate (40 g) concentrated Distillation of the residue

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cuprous iodide (198 mg; 1.04 mmole) was weighed into a 150 ml reaction tube purged with argon, and the inside of the tube was dried under reduced pressure. Then, the reaction tube was again purged with argon. Dry tetrahydrofuran (10 ml) and tributylphosphine (0.673 ml; 2.70 mmoles) were introduced into the reaction tube, and stirred at 19° C. with stirring to form a uniform solution. The solution was cooled to -78° C., and n-butyllithium (1.60M, 0.647 ml, 1.04 mmoles) was added, and the mixture was stirred at -78° C. for 10 minutes. Then, a solution of (R)-4-t-butyldimethylsiloxy-2-cyclopentenone (200 mg, 0.942 mmole) in tetrahydrofuran (15 ml) was added dropwise at -78° C. over 0.8 hours using a syringe drive. The mixture was stirred at -78° C. for 10 minutes. Then, hexamethylphosphoric triamide (2 ml) was added, and the mixture was stirred for 40 minutes at -78° C. Tributyltin chloride (0.28 ml, 1.04 mmole) was added, and the temperature was raised to -30° C. A solution of 1-bromo-2-octyne (197 mg, 1.04 mmole) in tetrahydrofuran (2 ml) was added, and the mixture was stirred for 17.5 hours. Ether (10 ml) was added to the reaction mixture, and the mixture was successively washed with a saturated aqueous ammonium chloride solution (10 ml), a saturated aqueous potassium thiocyanate solution (10 ml) and a saturated aqueous sodium chloride solution (10 ml). The separated organic layer was dried over anhydrous sodium sulfate. The dried product was filtered and concentrated under reduced pressure. The resulting crude product was separated by silica gel column chromatography (Merck 7734, 6% water, 20 g; hexane:ethyl acetate=30:l) to give (2R,3R,4R)-3-butyl-4-t-butyldimethylsiloxy-2-(2-octynyl)cyclopentanone (58.8 mg, 0.155 mmole, 16%) which coincided with the product obtained in (i) above. purged with argon the inside of the tube was dried under reduced pressure Then, the reaction tube was again purged with argon with stirring to form a uniform solution The solution was cooled to -78° C. the mixture was stirred at -78° C. for 10 minutes The mixture was stirred at -78° C. for 10 minutes the mixture was stirred for 40 minutes at -78° C the temperature was raised to -30° C the mixture was stirred for 17.5 hours the mixture was successively washed with a saturated aqueous ammonium chloride solution (10 ml) The separated organic layer was dried over anhydrous sodium sulfate The dried product was filtered concentrated under reduced pressure The resulting crude product was separated by silica gel column chromatography (Merck 7734, 6% water, 20 g; hexane:ethyl acetate=30:l)

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

Procedure: Under argon atmosphere, anhydrous pyridine (0.4 ml, 4.9 mmol) was added to a solution of 2-octyne-1-ol (9.4658 g, 75 mmol) in anhydrous ether (50 ml). To the mixture, there was dropwise added phosphorus tribromide (2.35 ml, 25.0 mmol) at -30° C. to -35° C., and the resulting reaction mixture was stirred for one hour. The mixture was then stirred at room temperature for one hour. Brine (100 ml) was added to the reaction mixture followed by extraction with ether (50 ml×4). The organic layers were combined, washed with saturated aqueous sodium hydrogencarbonate solution (150 ml), with water (150 ml) and with brine (150 ml), and dried over anhydrous sodium sulfate (40 g) to concentrate. The residue was distilled (b.p.=53°-58° C. at 0.39 mmHg), yielding a colorless oil, 1-bromo-2-octyne (9.1493 g, 63% yield). The structure was confirmed by the following data. at -30° C. to -35° C. the resulting reaction mixture The mixture was then stirred at room temperature for one hour followed by extraction with ether (50 ml×4) washed with saturated aqueous sodium hydrogencarbonate solution (150 ml), with water (150 ml) and with brine (150 ml) dried over anhydrous sodium sulfate (40 g) to concentrate The residue was distilled (b.p.=53°-58° C. at 0.39 mmHg)

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

Procedure: A mixture of 5 g. of 1-bromo-2-octyne, 7 g. of potassium cyanide and 35 ml. of dimethylsulfoxide is stirred and heated under nitrogen for about 2.5 hrs. at reflux temperature. The mixture is then poured into water and extracted with ether. The ether extract is washed with water, than with saturated aqueous sodium chloride, dried over sodium sulfate, and evaporated under reduced pressure leaving a residue comprising 3-nonynenitrile. The thus obtained residue is mixed with 45 ml. of 25% hydrogen chloride in methanol containing 0.5 ml. of water while cooling in an ice bath. The ice is allowed to melt and the mixture is stirred for about 18 hrs., then is poured into water and extracted with ether. The ether extract is washed with water, aqueous sodium bicarbonate, and saturated aqueous sodium chloride, dried over sulfate, and evaporated under reduced pressure leaving a residue comprising methyl 3-nonynoate. A mixture of the thus obtained methyl 3-nonynoate, 500 mg. of 5% palladium-barium sulfate catalyst and 40 ml. of pyridine is shaken under hydrogen for about 2 hrs., until the uptake of hydrogen practically ceases. The mixture is then filtered, diluted with water, and extracted with ether. The ether extract is washed with water, dilute hydrochloric acid, and aqueous sodium bicarbonate, then is dried over sodium sulfate and evaporated to leave a residue comprising methyl 3-nonenoate. A mixture of 5 g heated under nitrogen for about 2.5 hrs at reflux temperature extracted with ether The ether extract is washed with water, than with saturated aqueous sodium chloride dried over sodium sulfate evaporated under reduced pressure

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

Procedure: A solution of 7-hydroxycoumarin (0.324 g, 1.99 mmol) and 1-bromo-2-octyne (0.378 g, 1.99 mmol) in 200 ml of acetone was heated under reflux in the presence of anhydrous potassium carbonate (3 grams) for 24 hours. After the reflux period, the reaction mixture was cooled, filtered and the collected solid was washed with fresh acetone. The acetone washings and the filtrate were combined and the solvent evaporated under reduced pressure to yield a pale yellow viscous liquid. The crude product was dissolved in a minimum amount of ethyl acetate and petroleum ether added until the solution became cloudy. The cloudy solution was concentrated under reduced pressure and a white precipitate formed. This precipitate was collected by vacuum filtration and recrystallized from aqueous methanol to yield the title compound as shiny, colorless plates, m.p. 74°-75° C., 0.245 g, 50%. 1H-NMR: 0.8-2.2 (m, 11H, (CH2)4CH3), 4.7 (t, 2H, OCH2C C), 6.2 (d, 1H, C3 --H J=9.3 Hz), 6.8 (dd, 1H, C6 --H), 6.9 (d, 1H, C8 --H, J=2.1 Hz), 7.4 (dd, 1H, C5 --H, J=8.1 Hz), 7.6 (d, 1H, C4 --H, J=9.3 Hz). After the reflux period, the reaction mixture was cooled filtered the collected solid was washed with fresh acetone the solvent evaporated under reduced pressure to yield a pale yellow viscous liquid added until the solution The cloudy solution was concentrated under reduced pressure a white precipitate formed This precipitate was collected by vacuum filtration recrystallized from aqueous methanol