1-bromo-4-ethenoxybenzene

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: 39.0 g (176 mmol) 1-Bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled to 0° C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol/l in hexane) are added and stirring is continued for 2 h at 0° C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The organic phases are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution extracted with TBME (2×) washed with brine dried over MgSO4 the solvent is removed in vacuo The crude product is purified by column chromatography (silica gel, PE)

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

Procedure: With reference to the document (Tetrahedron Lett., (1998), 39, 8621-8624), the following cyclopropanization was conducted. Diethyl zinc (1.0 M hexane solution, 250 mL, 250 mmol) was added to dichloromethane (250 mL), and a solution of dichloromethane (120 mL) containing trifluoroacetic acid (19.2 mL, 249 mmol) was added thereto under ice-cooling over 100 minutes. The mixture was further stirred for 1 hour. Then, a solution of dichloromethane (100 mL) containing chloroiodomethane (20.1 mL, 250 mmol) was added thereto under ice-cooling over 40 minutes, and a solution of dichloromethane (120 mL) containing 1-bromo-4-(vinyloxy)benzene (32.8 g, 165 mmol) prepared in Example 6 (6b) was further added thereto at the same temperature over 20 minutes. The mixture was stirred at room temperature for 1.5 hours. Then, 0.1 N hydrochloric acid (400 mL) was added to the reaction solution. The mixture was stirred for 30 minutes, filtered through Celite, and washed with hexane (200 mL). The filtrate and the hexane washing solution were combined. The organic layer was washed with 0.1N hydrochloric acid (100 mL) and then with saturated brine (100 mL) containing about 1 g of sodium sulfite twice. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to give 36.0 g of 1-bromo-4-(cyclopropyloxy)benzene (yellow oil). was added under ice-cooling over 100 minutes was added under ice-cooling over 40 minutes was further added at the same temperature over 20 minutes The mixture was stirred at room temperature for 1.5 hours The mixture was stirred for 30 minutes filtered through Celite washed with hexane (200 mL) The organic layer was washed with 0.1N hydrochloric acid (100 mL) with saturated brine (100 mL) containing about 1 g of sodium sulfite twice The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: With reference to the document (Tetrahedron Lett., (1998), 39, 8621-8624), the following cyclopropanization was conducted. Diethyl zinc (1.0 M hexane solution, 250 mL, 250 mmol) was added to dichloromethane (250 mL), and a solution of dichloromethane (120 mL) containing trifluoroacetic acid (19.2 mL, 249 mmol) was added thereto under ice-cooling over 100 minutes. The mixture was further stirred for 1 hour. Then, a solution of dichloromethane (100 mL) containing chloroiodomethane (20.1 mL, 250 mmol) was added thereto under ice-cooling over 40 minutes, and a solution of dichloromethane (120 mL) containing 1-bromo-4-(vinyloxy)benzene (32.8 g, 165 mmol) prepared in Example 6 (6b) was further added thereto at the same temperature over 20 minutes. The mixture was stirred at room temperature for 1.5 hours. Then, 0.1 N hydrochloric acid (400 mL) was added to the reaction solution. The mixture was stirred for 30 minutes, filtered through Celite, and washed with hexane (200 mL). The filtrate and the hexane washing solution were combined. The organic layer was washed with 0.1N hydrochloric acid (100 mL) and then with saturated brine (100 mL) containing about 1 g of sodium sulfite twice. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to give 36.0 g of 1-bromo-4-(cyclopropyloxy)benzene (yellow oil). was added under ice-cooling over 100 minutes was added under ice-cooling over 40 minutes was further added at the same temperature over 20 minutes The mixture was stirred at room temperature for 1.5 hours The mixture was stirred for 30 minutes filtered through Celite washed with hexane (200 mL) The organic layer was washed with 0.1N hydrochloric acid (100 mL) with saturated brine (100 mL) containing about 1 g of sodium sulfite twice The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: Tert-Butoxypotassium (33.7 g, 300 mmol) was added to a solution of tetrahydrofuran (hereinafter THF) (250 mL) containing 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 6 (6a) over 10 minutes at −10° C. The mixture was stirred at room temperature for 21 hours, and water (500 mL) was added thereto. The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in hexane (100 mL), and the precipitated insoluble substance was removed by filtration. The insoluble substance was further washed with hexane (5 mL) five times. The filtrates were combined, concentrated, and purified by silica gel column chromatography (hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in hexane (100 mL) the precipitated insoluble substance was removed by filtration The insoluble substance was further washed with hexane (5 mL) five times concentrated purified by silica gel column chromatography (hexane)

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

Procedure: To mixture of 1-bromo-4-vinyloxybenzene (11.5 g, 58 mmol), chloroiodomethane (41 g, 232 mmol) and dichloroethane (180 mL) was added diethylzinc (15% solution in hexanes-95.5 mL, 116 mmol) over 3 h at 0° C. After 30 min stirring, NH4Cl solution (200 mL, aq. sat.) and light petrol (300 mL) was added. The organic phase was separated and concentrated in vacuo (8 bar, 50° C.). The residue was redissolved in light petrol and the insoluble material was filtered off. The filtrate was concentrated to afford sub-title compound (11.7 g, 94%). The organic phase was separated concentrated in vacuo (8 bar, 50° C.) The residue was redissolved in light petrol the insoluble material was filtered off The filtrate was concentrated

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

Procedure: To a solution of 1-bromo-4-(2-bromoethoxy)benzene (19.9 g, 100 mmol; see step (a) above) in THF (120 mL) was portion-wise added t-BuOK (14.0 g, 125 mmol) over 10 min at 0° C. After stirring at room temperature for 16 h, the mixture was diluted with water (400 mL) and the product was extracted with light petrol (4×100 mL). The combined organic extracts were washed with brine, dried (Na2SO4), concentrated and distilled under vacuum to yield the sub-title compound (11.5 g, 58%). the product was extracted with light petrol (4×100 mL) The combined organic extracts were washed with brine dried (Na2SO4) concentrated distilled under vacuum

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

Procedure: With reference to the document (Tetrahedron Lett., (1998), 39, 8621-8624), the following cyclopropanization was conducted. Diethyl zinc (1.0 M hexane solution, 250 mL, 250 mmol) was added to dichloromethane (250 mL), and a solution of dichloromethane (120 mL) containing trifluoroacetic acid (19.2 mL, 249 mmol) was added thereto under ice-cooling over 100 minutes. The mixture was further stirred for 1 hour. Then, a solution of dichloromethane (100 mL) containing chloroiodomethane (20.1 mL, 250 mmol) was added thereto under ice-cooling over 40 minutes, and a solution of dichloromethane (120 mL) containing 1-bromo-4-(vinyloxy)benzene (32.8 g, 165 mmol) prepared in Example 6 (6b) was further added thereto at the same temperature over 20 minutes. The mixture was stirred at room temperature for 1.5 hours. Then, 0.1 N hydrochloric acid (400 mL) was added to the reaction solution. The mixture was stirred for 30 minutes, filtered through Celite, and washed with hexane (200 mL). The filtrate and the hexane washing solution were combined. The organic layer was washed with 0.1 N hydrochloric acid (100 mL) and then with saturated brine (100 mL) containing about 1 g of sodium sulfite twice. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to give 36.0 g of 1-bromo-4-(cyclopropyloxy)benzene (yellow oil). was added under ice-cooling over 100 minutes was added under ice-cooling over 40 minutes was further added at the same temperature over 20 minutes The mixture was stirred at room temperature for 1.5 hours The mixture was stirred for 30 minutes filtered through Celite washed with hexane (200 mL) The organic layer was washed with 0.1 N hydrochloric acid (100 mL) with saturated brine (100 mL) containing about 1 g of sodium sulfite twice The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: With reference to the document (Tetrahedron Lett., (1998), 39, 8621-8624), the following cyclopropanization was conducted. Diethyl zinc (1.0 M hexane solution, 250 mL, 250 mmol) was added to dichloromethane (250 mL), and a solution of dichloromethane (120 mL) containing trifluoroacetic acid (19.2 mL, 249 mmol) was added thereto under ice-cooling over 100 minutes. The mixture was further stirred for 1 hour. Then, a solution of dichloromethane (100 mL) containing chloroiodomethane (20.1 mL, 250 mmol) was added thereto under ice-cooling over 40 minutes, and a solution of dichloromethane (120 mL) containing 1-bromo-4-(vinyloxy)benzene (32.8 g, 165 mmol) prepared in Example 6 (6b) was further added thereto at the same temperature over 20 minutes. The mixture was stirred at room temperature for 1.5 hours. Then, 0.1 N hydrochloric acid (400 mL) was added to the reaction solution. The mixture was stirred for 30 minutes, filtered through Celite, and washed with hexane (200 mL). The filtrate and the hexane washing solution were combined. The organic layer was washed with 0.1 N hydrochloric acid (100 mL) and then with saturated brine (100 mL) containing about 1 g of sodium sulfite twice. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to give 36.0 g of 1-bromo-4-(cyclopropyloxy)benzene (yellow oil). was added under ice-cooling over 100 minutes was added under ice-cooling over 40 minutes was further added at the same temperature over 20 minutes The mixture was stirred at room temperature for 1.5 hours The mixture was stirred for 30 minutes filtered through Celite washed with hexane (200 mL) The organic layer was washed with 0.1 N hydrochloric acid (100 mL) with saturated brine (100 mL) containing about 1 g of sodium sulfite twice The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: Tert-Butoxypotassium (33.7 g, 300 mmol) was added to a solution of tetrahydrofuran (hereinafter THF) (250 mL) containing 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 6 (6a) over 10 minutes at −10° C. The mixture was stirred at room temperature for 21 hours, and water (500 mL) was added thereto. The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in hexane (100 mL), and the precipitated insoluble substance was removed by filtration. The insoluble substance was further washed with hexane (5 mL) five times. The filtrates were combined, concentrated, and purified by silica gel column chromatography (hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in hexane (100 mL) the precipitated insoluble substance was removed by filtration The insoluble substance was further washed with hexane (5 mL) five times concentrated purified by silica gel column chromatography (hexane)

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

Procedure: 39.0 g (176 mmol) 1-Bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled to 0° C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol/l in hexane) are added and stirring is continued for 2 h at 0° C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The organic phases are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution extracted with TBME (2×) washed with brine dried over MgSO4 the solvent is removed in vacuo The crude product is purified by column chromatography (silica gel, PE)