1-bromo-2-propan-2-yloxybenzene

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

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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspended solution of Mg chips (10.07 g, 0.414 mol) in anhydrous ether (150 mL) at 22° C. under argon was added ca. 0.15 mL of 1,2-dibromoethane. Then 43.7 g (0.200 mol) of XIV in 200 mL of ether was added dropwise. After 50% of the aryl halide was added, the reaction began to reflux vigorously. The flask was cooled in an ice bath. After the refluxing had subsided somewhat, the ice bath was removed and the remaining aryl halide was added over a 1.5 h period. The resultant Grignard reagent was cooled in a dry ice/ether bath for 2 h and then treated with 34.0 mL (0.221 mol) of 98% 1-carbethoxy-4-piperidone. Upon complete addition of ketone, the reaction mixture was allowed to warm to 22° C. and stirred for 2 h. The reaction was then quenched with cold aqueous ammonium chloride which resulted in an emulsion. Addition of 1M aqueous HCl solution separated the two layers. The aqueous phase was extracted with additional ether and the combined organic solution was washed with 10% aqueous sodium bisulfite, 1.0M HCl, saturated NaHCO3, and dried (K2CO3). Filtration concentration yielded 56.36 g of XV as a yellow viscous oil which was carried on without further purification The structure of this oil was supported by 1H NMR. to reflux vigorously The flask was cooled in an ice bath the ice bath was removed the remaining aryl halide was added over a 1.5 h period The resultant Grignard reagent was cooled in a dry ice/ether bath for 2 h The reaction was then quenched with cold aqueous ammonium chloride which resulted in an emulsion separated the two layers The aqueous phase was extracted with additional ether the combined organic solution was washed with 10% aqueous sodium bisulfite, 1.0M HCl, saturated NaHCO3 dried (K2CO3) Filtration concentration

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspended solution of Mg chips (10.07 g, 0.414 mol) in anhydrous ether (150 mL) at 22° C. under argon was added ca. 0.15 mL of 1,2-dibromoethane. Then 43.7 g (0.200 mol) of XIV in 200 mL of ether was added dropwise. After 50% of the aryl halide was added, the reaction began to reflux vigorously. The flask was cooled in an ice bath. After the refluxing had subsided somewhat, the ice bath was removed and the remaining aryl halide was added over a 1.5 h period. The resultant Grignard reagent was cooled in a dry ice/ether bath for 2 h and then treated with 34.0 mL (0.221 mol) of 98% 1-carbethoxy-4-piperidone. Upon complete addition of ketone, the reaction mixture was allowed to warm to 22° C. and stirred for 2 h. The reaction was then quenched with cold aqueous ammonium chloride which resulted in an emulsion. Addition of 1M aqueous HCl solution separated the two layers. The aqueous phase was extracted with additional ether and the combined organic solution was washed with 10% aqueous sodium bisulfite, 1.0M HCl, saturated NaHCO3, and dried (K2CO3). Filtration concentration yielded 56.36 g of XV as a yellow viscous oil which was carried on without further purification The structure of this oil was supported by 1H NMR. to reflux vigorously The flask was cooled in an ice bath the ice bath was removed the remaining aryl halide was added over a 1.5 h period The resultant Grignard reagent was cooled in a dry ice/ether bath for 2 h The reaction was then quenched with cold aqueous ammonium chloride which resulted in an emulsion separated the two layers The aqueous phase was extracted with additional ether the combined organic solution was washed with 10% aqueous sodium bisulfite, 1.0M HCl, saturated NaHCO3 dried (K2CO3) Filtration concentration

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

Procedure: A mixture of 2-bromophenol (23.2 mL, 0.20 mol), potassium carbonate (33.2 g, 0.24 mol) and 2-bromopropane (28.0 mL, 0.30 mol) in dimethylformamide (200 mL) was stirred in a preheated oil bath (60° C.) for 5 h. The cooled reaction mixture was then partitioned between ether and water. The layers were separated and the aqueous phase was extracted with ether. The combined organic solution was washed with copious amounts of water, 3N aqueous NaOH, dried (MgSO4), filtered and concentrated in vacuo to furnish 39.3 g (91%) of XIV as a pale yellow oil which was carried on without further purification. The structure was supported by GC/MS and 90 MHz 1H NMR. The cooled reaction mixture was then partitioned between ether and water The layers were separated the aqueous phase was extracted with ether The combined organic solution was washed with copious amounts of water, 3N aqueous NaOH dried (MgSO4) filtered concentrated in vacuo

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

Procedure: Prepare a stirred mixture of ortho-bromo-phenol (25.951 g, 17.4 mL, 0.15 mole) and potassium carbonate (20.70 g, 0.16 mole) in 175 mL isopropanol at ambient temperature under argon. Slowly add isopropyl iodide (22.2 g, 16.00 mL), heat at reflux and stir the mixture overnight. Cool to ambient temperature then filter, condensing the filtrate on a rotary evaporator. Dissolve the residual oil in diethyl ether (300 mL) and twice extract with 100 mL 50% sodium hyroxide. Separate, wash with brine and concentrate on a rotary evaporator to give a pale yellow liquid. Distill on the Kugelrohr (0.05 mm, 100°-120° C.) to obtain the title compound as an oil. (24.21 g, 75%). Prepare at reflux then filter condensing the filtrate on a rotary evaporator Dissolve the residual oil in diethyl ether (300 mL) twice extract with 100 mL 50% sodium hyroxide Separate wash with brine concentrate on a rotary evaporator to give a pale yellow liquid Distill on the Kugelrohr (0.05 mm, 100°-120° C.)

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

Procedure: Prepare a stirred mixture of ortho-bromo-phenol (25.951 g, 17.4 mL, 0.15 mole) and potassium carbonate (20.70 g, 0.16 mole) in 175 mL isopropanol at ambient temperature under argon. Slowly add isopropyl iodide (22.2 g, 16.00 mL), heat at reflux and stir the mixture overnight. Cool to ambient temperature then filter, condensing the filtrate on a rotary evaporator. Dissolve the residual oil in diethyl ether (300 mL) and twice extract with 100 mL 50% sodium hyroxide. Separate, wash with brine and concentrate on a rotary evaporator to give a pale yellow liquid. Distill on the Kugelrohr (0.05 mm, 100°-120° C.) to obtain the title compound as an oil. (24.21 g, 75%). Prepare at reflux then filter condensing the filtrate on a rotary evaporator Dissolve the residual oil in diethyl ether (300 mL) twice extract with 100 mL 50% sodium hyroxide Separate wash with brine concentrate on a rotary evaporator to give a pale yellow liquid Distill on the Kugelrohr (0.05 mm, 100°-120° C.)

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

Procedure: 2-Bromophenol (500 mg, 2.9 mmol) was dissolved in dry dimethylformamide (5 mL) under a dry nitrogen atmosphere. Powdered dry cesium carbonate (1.41. g, 4.34 mmol) was added, followed by the addition of 2-bromopropane (404 μL, 4.05 mmol) over a 2 min period. The mixture was stirred at room temperature overnight. Water (50 mL) was added and the mixture extracted with ethyl acetate (2×50 mL). The combined extracts were successively washed with water (25 mL) and saturated salt solution (25 mL) and dried over anhydrous magnesium sulfate. The dried solution was filtered and the solvents removed rotoevaporation to yield the title compound as an oil (522 mg, 84% yield). the mixture extracted with ethyl acetate (2×50 mL) The combined extracts were successively washed with water (25 mL) and saturated salt solution (25 mL) dried over anhydrous magnesium sulfate The dried solution was filtered the solvents removed rotoevaporation

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

Procedure: The title compound was prepared as in Example 257A but employing 2-iso-propyloxybromobenzene in lieu of 1-bromo-3-isopropoxybenzene. Purification on silica, gel with 10% ether/hexane afforded the title compound (2.3 g, 70%). The title compound was prepared as in Example 257A Purification on silica, gel with 10% ether/hexane

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

Procedure: The title compound was prepared in a manner similar to Preparation 1A except that piperazine was coupled to 1-bromo-2-isopropoxy-benzene. LRMS (ESI+): 221.4 (M+1)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspended solution of Mg chips (10.07 g, 0.414 mol) in anhydrous ether (150 mL) at 22° C. under argon was added ca. 0.15 mL of 1,2-dibromoethane. Then 43.7 g (0.200 mol) of XIV in 200 mL of ether was added dropwise. After 50% of the aryl halide was added, the reaction began to reflux vigorously. The flask was cooled in an ice bath. After the refluxing had subsided somewhat, the ice bath was removed and the remaining aryl halide was added over a 1.5 h period. The resultant Grignard reagent was cooled in a dry ice/ether bath for 2 h and then treated with 34.0 mL (0.221 mol) of 98% 1-carbethoxy-4-piperidone. Upon complete addition of ketone, the reaction mixture was allowed to warm to 22° C. and stirred for 2 h. The reaction was then quenched with cold aqueous ammonium chloride which resulted in an emulsion. Addition of 1M aqueous HCl solution separated the two layers. The aqueous phase was extracted with additional ether and the combined organic solution was washed with 10% aqueous sodium bisulfite, 1.0M HCl, saturated NaHCO3, and dried (K2CO3). Filtration concentration yielded 56.36 g of XV as a yellow viscous oil which was carried on without further purification The structure of this oil was supported by 1H NMR. to reflux vigorously The flask was cooled in an ice bath the ice bath was removed the remaining aryl halide was added over a 1.5 h period The resultant Grignard reagent was cooled in a dry ice/ether bath for 2 h The reaction was then quenched with cold aqueous ammonium chloride which resulted in an emulsion separated the two layers The aqueous phase was extracted with additional ether the combined organic solution was washed with 10% aqueous sodium bisulfite, 1.0M HCl, saturated NaHCO3 dried (K2CO3) Filtration concentration

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

Procedure: A mixture of 2-bromophenol (23.2 mL, 0.20 mol), potassium carbonate (33.2 g, 0.24 mol) and 2-bromopropane (28.0 mL, 0.30 mol) in dimethylformamide (200 mL) was stirred in a preheated oil bath (60° C.) for 5 h. The cooled reaction mixture was then partitioned between ether and water. The layers were separated and the aqueous phase was extracted with ether. The combined organic solution was washed with copious amounts of water, 3N aqueous NaOH, dried (MgSO4), filtered and concentrated in vacuo to furnish 39.3 g (91%) of XIV as a pale yellow oil which was carried on without further purification. The structure was supported by GC/MS and 90 MHz 1H NMR. The cooled reaction mixture was then partitioned between ether and water The layers were separated the aqueous phase was extracted with ether The combined organic solution was washed with copious amounts of water, 3N aqueous NaOH dried (MgSO4) filtered concentrated in vacuo