2-[(2-bromophenyl)methoxy]oxane

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 mixed solution of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (2.71 g, 0.01 mol) and dry THF (8 ml) was added dropwise at 50° to 60° C. over 20 minutes to a solution prepared by adding dry THF (2 ml) and ethyl bromide (0.1 ml) to magnesium (0.36 g, 0.015 mol) in a stream of nitrogen. After completion of the addition, the mixture was stirred at 50° to 60° C. for 1 hour and cooled to room temperature. After cooling, the mixture was added dropwise to a mixed solution of oxalyl chloride (1.90 g, 0.015 mol) and dry THF (30 ml) at below -50° C. over 15 minutes. Then, the mixture was stirred at -60° to -70° C. for 40 minutes. A 40% methylamine-methanol solution (4.66 g, 0.06 mol) was added to the reaction mixture, and the mixture was stirred at -20° to -10° C. for 30 minutes. After completion of the reaction, water (150 ml) was added, and the mixture was extracted with ether (150 ml). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to obtain N-methyl-2-oxo-2-[2-(2-tetrahydropyranyloxymethyl)phenyl]acetamide(1.18 g, Yield: 42.5%) as a colorless oil. prepared After completion of the addition After cooling Then, the mixture was stirred at -60° to -70° C. for 40 minutes the mixture was stirred at -20° to -10° C. for 30 minutes was added the mixture was extracted with ether (150 ml) The extract was washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane)

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

Procedure: Magnesium (2.67 g, 0.11 mol) and bromoethane (0.2 ml) were added to a mixed solution of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (27.11 g, 0.10 mol) and THF (50 ml) under an atmosphere of nitrogen gas. The mixture was stirred at room temperature for 1 hour to prepare a Grignard reagent. The Grignard reagent was added dropwise to a mixed solution of diethyl oxalate (29.23 g, 0.20 mol) and THF (100 ml) cooled to -78° C. The mixture was stirred at -78° C. for 1 hour, water (150 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to obtain ethyl 2-oxo-2-[2-(2-tetrahydropyranyloxymethyl)phenyl]acetate (22.60 g, Yield: 77.3%) as a colorless oil. cooled to -78° C The mixture was stirred at -78° C. for 1 hour the mixture was extracted with ether (200 ml) The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane)

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

Procedure: Pyridinium p-toluenesulfonate (0.30 g, 0.0012 mol) was added to a solution of 2-bromobenzyl alcohol (25 g, 0.134 mol) in dichloromethane (100 ml), and the mixture was stirred at room temperature. To this mixture was added 3,4-dihydro-2H-pyrane (16.86 g, 0.20 mol). After the resulting mixture was stirred at room temperature for 2 hours, a saturated aqueous solution (200 ml) of sodium bicarbonate was added. The mixture was extracted with dichloromethane (200 ml). After the mixture was dried over anhydrous magnesium sulfate, the solvent was evaporated to obtain the desired compound 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (36.00 g, Yield: 99.3%) as an oil. After the resulting mixture was stirred at room temperature for 2 hours The mixture was extracted with dichloromethane (200 ml) After the mixture was dried over anhydrous magnesium sulfate the solvent was evaporated

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil. The mixture was stirred at −60° C. to room temperature for 1 hour the mixture was extracted with ether (200 ml) The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/n-hexane)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil. The mixture was stirred at −60° C. to room temperature for 1 hour the mixture was extracted with ether (200 ml) The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/n-hexane)

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

Procedure: Pyridinium p-toluenesulfonate (0.30 g, 0.0012 mol) was added to a solution of 2-bromobenzylalcohol (25 g, 0.134 mol) in dichloromethane (100 ml), and the mixture was stirred at room temperature. 3,4-Dihydro-2H-pyran (16.86 g, 0.20 mol) was added thereto. The mixture was stirred at room temperature for 2 hours. Then, saturated aqueous sodium bicarbonate solution (200 ml) was added, and the mixture was extracted with dichloromethane (200 ml). After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the desired 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (36.00 g, yield: 99.3%) as an oil. The mixture was stirred at room temperature for 2 hours the mixture was extracted with dichloromethane (200 ml) After drying over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: Pyridinium p-toluenesulfonate (0.30 g, 0.0012 mol) was added to a solution of 2-bromobenzylalcohol (25 g, 0.134 mol) in dichloromethane (100 ml), and the mixture was stirred at room temperature. 3,4-Dihydro-2H-pyran (16.86 g, 0.20 mol) was added thereto. The mixture was stirred at room temperature for 2 hours. Then, saturated aqueous sodium bicarbonate solution (200 ml) was added, and the mixture was extracted with dichloromethane (200 ml). After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the desired 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (36.00 g, yield: 99.3%) as an oil. The mixture was stirred at room temperature for 2 hours the mixture was extracted with dichloromethane (200 ml) After drying over anhydrous magnesium sulfate the solvent was evaporated

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at -60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil. The mixture was stirred at -60° C. to room temperature for 1 hour the mixture was extracted with ether (200 ml) The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/n-hexane)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at -60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil. The mixture was stirred at -60° C. to room temperature for 1 hour the mixture was extracted with ether (200 ml) The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/n-hexane)