5-bromopentoxybenzene

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

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

Procedure: To a well-stirred suspension of sodium hydride (15.3 g, 0.32 mol; 50% oil dispersion) in dry DMF (500 ml) containing (25 g, 0.26 mol), was added dropwise 1,5-dibromopentane (122.3 g, 0.53 mol). After the addition was complete, the reaction mixture was stirred at 60°-70° C. for 4 hours. Most of the DMF was next removed under reduced pressure, and the residue was dissolved in ethyl acetate (250 ml). The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine. After drying the organics over anhydrous magnesium sulfate, all volatiles were removed. The residual yellow liquid was then distilled under reduced pressure, and the pure product was collected at 118°-125° C./1 mm as a clear colorless liquid (26 g, 40% yield). containing (25 g, 0.26 mol) After the addition Most of the DMF was next removed under reduced pressure the residue was dissolved in ethyl acetate (250 ml) The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine After drying the organics over anhydrous magnesium sulfate all volatiles were removed The residual yellow liquid was then distilled under reduced pressure

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

Procedure: To a mixture of 5 phenoxy pentyl bromide (122.0 g, 0.5 mol) and 2-phenylcyclohexanone (104.4 g, 0.6 mol) in 1.5 L THF, NaH (0.55 mol, 24.0 g) was added portionwise, keeping the temperature between 25° to 30° C. After most of the H2 evolution had ceased, the reaction mixture was heated to reflux for 16 hours under a N2 atmosphere. After cooling to room temperature, 50 mL isopropanol was added and the mixture was concentrated in vacuo to half its volume. This residue was diluted with 2 L ether and 1 L H2O. The layers were separated and the aqueous layer was washed one time with 500 mL ether. The combined organic layers were washed two times each with 500 mL H2O, dried (MgSO4), and concentrated in vacuo to give a solid. Recrystallization from petroleum ether yielded 27.5 g (16.4%), mp 69°-72° C., of the desired product. was added portionwise between 25° to 30° C the reaction mixture was heated to reflux for 16 hours under a N2 atmosphere the mixture was concentrated in vacuo to half its volume This residue was diluted with 2 L ether and 1 L H2O The layers were separated the aqueous layer was washed one time with 500 mL ether The combined organic layers were washed two times each with 500 mL H2O dried (MgSO4) concentrated in vacuo to give a solid Recrystallization from petroleum ether yielded 27.5 g (16.4%), mp 69°-72° C.

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

Procedure: To a mixture of 5 phenoxy pentyl bromide (122.0 g, 0.5 mol) and 2-phenylcyclohexanone (104.4 g, 0.6 mol) in 1.5 L THF, NaH (0.55 mol, 24.0 g) was added portionwise, keeping the temperature between 25° to 30° C. After most of the H2 evolution had ceased, the reaction mixture was heated to reflux for 16 hours under a N2 atmosphere. After cooling to room temperature, 50 mL isopropanol was added and the mixture was concentrated in vacuo to half its volume. This residue was diluted with 2 L ether and 1 L H2O. The layers were separated and the aqueous layer was washed one time with 500 mL ether. The combined organic layers were washed two times each with 500 mL H2O, dried (MgSO4), and concentrated in vacuo to give a solid. Recrystallization from petroleum ether yielded 27.5 g (16.4%), mp 69°-72° C., of the desired product. was added portionwise between 25° to 30° C the reaction mixture was heated to reflux for 16 hours under a N2 atmosphere the mixture was concentrated in vacuo to half its volume This residue was diluted with 2 L ether and 1 L H2O The layers were separated the aqueous layer was washed one time with 500 mL ether The combined organic layers were washed two times each with 500 mL H2O dried (MgSO4) concentrated in vacuo to give a solid Recrystallization from petroleum ether yielded 27.5 g (16.4%), mp 69°-72° C.

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

Procedure: To a well-stirred suspension of sodium hydride (15.3 g, 0.32 mol; 50% oil dispersion) in dry DMF (500 ml) containing (25 g, 0.26 mol), was added dropwise 1,5-dibromopentane (122.3 g, 0.53 mol). After the addition was complete, the reaction mixture was stirred at 60°-70° C. for 4 hours. Most of the DMF was next removed under reduced pressure, and the residue was dissolved in ethyl acetate (250 ml). The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine. After drying the organics over anhydrous magnesium sulfate, all volatiles were removed. The residual yellow liquid was then distilled under reduced pressure, and the pure product was collected at 118°-125° C./1 mm as a clear colorless liquid (26 g, 40% yield). containing (25 g, 0.26 mol) After the addition Most of the DMF was next removed under reduced pressure the residue was dissolved in ethyl acetate (250 ml) The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine After drying the organics over anhydrous magnesium sulfate all volatiles were removed The residual yellow liquid was then distilled under reduced pressure

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

Procedure: To a well-stirred suspension of sodium hydride (15.3 g, 0.32 mol; 50% oil dispersion) in dry DMF (500 ml) containing (25 g, 0.26 mol), was added dropwise 1,5-dibromopentane (122.3 g, 0.53 mol). After the addition was complete, the reaction mixture was stirred at 60°-70° C. for 4 hours. Most of the DMF was next removed under reduced pressure, and the residue was dissolved in ethyl acetate (250 ml). The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine. After drying the organics over anhydrous magnesium sulfate, all volatiles were removed. The residual yellow liquid was then distilled under reduced pressure, and the pure product was collected at 118°-125° C./1 mm as a clear colorless liquid (26 g, 40% yield). containing (25 g, 0.26 mol) After the addition Most of the DMF was next removed under reduced pressure the residue was dissolved in ethyl acetate (250 ml) The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine After drying the organics over anhydrous magnesium sulfate all volatiles were removed The residual yellow liquid was then distilled under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with (5-bromopentoxy)benzene (1.4 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material from dichloromethane extraction was purified by HPLC (dichloromethane-hexane; 4:1) to provide 0.9 g of analytically pure alpha-oxo-4-[[(5-phenoxy)pentyl]oxy]benzeneacetic acid methyl ester which failed to crystallize. The material from dichloromethane extraction was purified by HPLC (dichloromethane-hexane; 4:1)

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

Procedure: 2-Benzyl-1-(5-phenoxypentyl)piperidine hydrobromide. From a mixture of 2-benzylpiperidine hydrochloride (500 mg, 2.36 mmol), K2CO3 (652 mg, 4.72 mmol, ) and 1-bromo-5-phenoxypentane (860 mg, 3.54 mmol) in CH3CN (25 mL) there was obtained the free amine as a clear amber oil; (568 mg, 71%); 1H NMR (CDCl3), 1.15-1.90 (m, 12 H), 2.29-2.89 (m, 6 H), 3.08 (dd, J1=12.6 Hz, J2=3.3 Hz, 1 H), 3.97 (t, J=6.3 Hz, 2 H), 6.85-7.33 (m, 10 H).

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

Procedure: 2-Benzyl-1-(5-phenoxypentyl)piperidine hydrobromide. From a mixture of 2-benzylpiperidine hydrochloride (500 mg, 2.36 mmol), K2CO3 (652 mg, 4.72 mmol, ) and 1-bromo-5-phenoxypentane (860 mg, 3.54 mmol) in CH3CN (25 mL) there was obtained the free amine as a clear amber oil; (568 mg, 71%); 1H NMR (CDCl3), 1.15-1.90 (m, 12H), 2.29-2.89 (m, 6H), 3.08 (dd, J1=12.6 Hz, J2=3.3 Hz, 1H), 3.97 (t, J=6.3 Hz, 2H), 6.85-7.33 (m, 10H).

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

Procedure: Potassium carbonate (2.5 g) was mixed with a solution of 5-phenoxy-1-bromopentane (1.7 g, 0.006 mol) and the product of Example 1 (2.0 g, 0.006 mol) in methyl ethyl ketone (20 ml). The reaction mixture was stirred and refluxed under a nitrogen atmosphere for 4 hrs and then worked up according to the procedure described in Example 2. The residue was chromatographed on silica gel using 4% acetone/benzene as eluent to give 1.8 g (80%) of the title compound as an oil. refluxed under a nitrogen atmosphere for 4 hrs The residue was chromatographed on silica gel using 4% acetone/benzene as eluent

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

Procedure: To a mixture of 5 phenoxy pentyl bromide (122.0 g, 0.5 mol) and 2-phenylcyclohexanone (104.4 g, 0.6 mol) in 1.5 L THF, NaH (0.55 mol, 24.0 g) was added portionwise, keeping the temperature between 25° to 30° C. After most of the H2 evolution had ceased, the reaction mixture was heated to reflux for 16 hours under a N2 atmosphere. After cooling to room temperature, 50 mL isopropanol was added and the mixture was concentrated in vacuo to half its volume. This residue was diluted with 2 L ether and 1 L H2O. The layers were separated and the aqueous layer was washed one time with 500 mL ether. The combined organic layers were washed two times each with 500 mL H2O, dried (MgSO4), and concentrated in vacuo to give a solid. Recrystallization from petroleum ether yielded 27.5 g (16.4%), mp 69°-72° C., of the desired product. was added portionwise between 25° to 30° C the reaction mixture was heated to reflux for 16 hours under a N2 atmosphere the mixture was concentrated in vacuo to half its volume This residue was diluted with 2 L ether and 1 L H2O The layers were separated the aqueous layer was washed one time with 500 mL ether The combined organic layers were washed two times each with 500 mL H2O dried (MgSO4) concentrated in vacuo to give a solid Recrystallization from petroleum ether yielded 27.5 g (16.4%), mp 69°-72° C.

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

Procedure: To a well-stirred suspension of sodium hydride (15.3 g, 0.32 mol; 50% oil dispersion) in dry DMF (500 ml) containing (25 g, 0.26 mol), was added dropwise 1,5-dibromopentane (122.3 g, 0.53 mol). After the addition was complete, the reaction mixture was stirred at 60°-70° C. for 4 hours. Most of the DMF was next removed under reduced pressure, and the residue was dissolved in ethyl acetate (250 ml). The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine. After drying the organics over anhydrous magnesium sulfate, all volatiles were removed. The residual yellow liquid was then distilled under reduced pressure, and the pure product was collected at 118°-125° C./1 mm as a clear colorless liquid (26 g, 40% yield). containing (25 g, 0.26 mol) After the addition Most of the DMF was next removed under reduced pressure the residue was dissolved in ethyl acetate (250 ml) The organic extract was washed successively with a 5% sodium hydroxide solution, water and brine After drying the organics over anhydrous magnesium sulfate all volatiles were removed The residual yellow liquid was then distilled under reduced pressure