(2Z,6Z)-1-bromo-3,7,11-trimethyldodeca-2,6,10-triene

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:

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

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

Procedure: To a solution of 9.60 ml (68.5 mmol, 1.5 eq.) of diisopropylamine in 100 ml of THF at -78° C. under argon was added 28.2 ml (45.0 mmol, 1.0 eq.) of 1.6M n-butyllithium in hexanes over 20 minutes. After warming to 0° C. for 15 minutes, the solution was recooled to -78° C. and 6.05 ml (45 mmol, 1.0 eq) of t-butyl acetate was added over 20 minutes. After an additional 15 minutes, 16.0 ml (92 mmol, 2.05 eq.) of hexamethylphosphoramide (HMPA) was added, followed by a solution of 12.53 g (45.0 mmol) of Part A(1) farnesyl bromide in 100 ml of THF over 20 minutes. The reaction was stirred at -78° C. for 2.5 hours, quenched with saturated NH4Cl and allowed to warm to room temperature. After diluting with 400 ml of ethyl acetate, the mixture was washed with four 100 ml portions of water, and 200 ml of brine, dried over MgSO4 and evaporated to provide 12.96 g of crude product as a yellow oil. Purification by flash chromatography on 1 kg of silica gel, eluted with 1:9 ethyl acetate:petroleum ether afforded 9.39 g (65%) of title compound as a pale yellow oil. was recooled to -78° C. quenched with saturated NH4Cl to warm to room temperature After diluting with 400 ml of ethyl acetate the mixture was washed with four 100 ml portions of water, and 200 ml of brine dried over MgSO4 evaporated to provide 12.96 g of crude product as a yellow oil Purification by flash chromatography on 1 kg of silica gel eluted with 1:9 ethyl acetate

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

Procedure: A solution of 2.47 g of the above farnesyl bromide in 20 ml of dry dimethyformamide (DMF) at room temperature under argon was treated with 1.83 g (9.9 mmol, 1.1 eq.) of potassium phthalimide and stirred for 3 hours at room temperature. The solvent was removed under reduced pressure, the residue was triturated with 150 ml of ethyl ether, and the precipitate was filtered off. The ethereal solution was washed with 50 ml of H2O and 50 ml of brine, dried over MgSO4 and evaporated to yield 2.96 g of crude title compound as a milky oil. Purification by flash chromatography on 300 g of Merck 9385 silica, eluted with 7:93 ethyl acetate:petroleum ether afforded 2.56 g (81%) of the desired product as a colorless oil. The solvent was removed under reduced pressure the residue was triturated with 150 ml of ethyl ether the precipitate was filtered off The ethereal solution was washed with 50 ml of H2O and 50 ml of brine dried over MgSO4 evaporated to yield 2.96 g of crude title compound as a milky oil Purification by flash chromatography on 300 g of Merck 9385 silica eluted with 7:93 ethyl acetate

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

Procedure: A solution of 2.00 g (9.0 mmol) of (E,E)-farnesol in 20 ml of dry diethyl ether at 0° C. under argon in the dark was treated dropwise with a solution of 735 μl (4.0 mmol, 0.45 eq.) of PBr3 in 4 ml of dry diethyl ether. The resultant mixture was stirred at 0° C. for one hour, then quenched with H2O and separated. The organic phase was washed with 15 ml of NaHCO3, 15 ml of H2O, and 15 ml of brine, dried over MgSO4 and evaporated to provide 2.47 g of crude farnesyl bromide as a clear oil. quenched with H2O separated The organic phase was washed with 15 ml of NaHCO3, 15 ml of H2O, and 15 ml of brine dried over MgSO4 evaporated

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

Procedure: To a solution of 9.60 ml (68.5 mmol, 1.5 eq.) of diisopropylamine in 100 ml of THF at -78° C. under argon was added 28.2 ml (45.0 mmol, 1.0 eq.) of 1.6M n-butyllithium in hexanes over 20 minutes. After warming to 0° C. for 15 minutes, the solution was recooled to -78° C. and 6.05 ml (45 mmol, 1.0 eq) of t-butyl acetate was added over 20 minutes. After an additional 15 minutes, 16.0 ml (92 mmol, 2.05 eq.) of hexamethylphosphoramide (HMPA) was added, followed by a solution of 12.53 g (45.0 mmol) of Part A(1) farnesyl bromide in 100 ml of THF over 20 minutes. The reaction was stirred at -78° C. for 2.5 hours, quenched with saturated NH4Cl and allowed to warm to room temperature. After diluting with 400 ml of ethyl acetate, the mixture was washed with four 100 ml portions of water, and 200 ml of brine, dried over MgSO4 and evaporated to provide 12.96 g of crude product as a yellow oil. Purification by flash chromatography on 1 kg of silica gel, eluted with 1:9 ethyl acetate:petroleum ether afforded 9.39 g (65%) of title compound as a pale yellow oil. was recooled to -78° C. quenched with saturated NH4Cl to warm to room temperature After diluting with 400 ml of ethyl acetate the mixture was washed with four 100 ml portions of water, and 200 ml of brine dried over MgSO4 evaporated to provide 12.96 g of crude product as a yellow oil Purification by flash chromatography on 1 kg of silica gel eluted with 1:9 ethyl acetate

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

Procedure: A solution of 2.47 g of the above farnesyl bromide in 20 ml of dry dimethyformamide (DMF) at room temperature under argon was treated with 1.83 g (9.9 mmol, 1.1 eq.) of potassium phthalimide and stirred for 3 hours at room temperature. The solvent was removed under reduced pressure, the residue was triturated with 150 ml of ethyl ether, and the precipitate was filtered off. The ethereal solution was washed with 50 ml of H 0 and 50 ml of brine, dried over MgSO4 and evaporated to yield 2.96 g of crude title compound as a milky oil. Purification by flash chromatography on 300 g of Merck 9385 silica, eluted with 7:93 ethyl acetate:petroleum ether afforded 2.56 g (81%) of the desired product as a colorless oil. The solvent was removed under reduced pressure the residue was triturated with 150 ml of ethyl ether the precipitate was filtered off The ethereal solution was washed with 50 ml of H 0 and 50 ml of brine dried over MgSO4 evaporated to yield 2.96 g of crude title compound as a milky oil Purification by flash chromatography on 300 g of Merck 9385 silica eluted with 7:93 ethyl acetate

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

Procedure: A solution of 2.47 g of the above farnesyl bromide in 20 ml of dry dimethyformamide (DMF) at room temperature under argon was treated with 1.83 g (9.9 mmol, 1.1 eq.) of potassium phthalimide and stirred for 3 hours at room temperature. The solvent was removed under reduced pressure, the residue was triturated with 150 ml of ethyl ether, and the precipitate was filtered off. The ethereal solution was washed with 50 ml of H 0 and 50 ml of brine, dried over MgSO4 and evaporated to yield 2.96 g of crude title compound as a milky oil. Purification by flash chromatography on 300 g of Merck 9385 silica, eluted with 7:93 ethyl acetate:petroleum ether afforded 2.56 g (81%) of the desired product as a colorless oil. The solvent was removed under reduced pressure the residue was triturated with 150 ml of ethyl ether the precipitate was filtered off The ethereal solution was washed with 50 ml of H 0 and 50 ml of brine dried over MgSO4 evaporated to yield 2.96 g of crude title compound as a milky oil Purification by flash chromatography on 300 g of Merck 9385 silica eluted with 7:93 ethyl acetate