(2-methoxyphenyl)methanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3 g of the 3-(3,4-dimethoxyphenethyl)amino-2-hydroxypropionic acid prepared in Example I was added 200 ml of benzene and 20 ml of 2-methoxybenzyl alcohol. About 0.5 ml of concentrated HCl was added to catalyze the reaction. The reaction mixture was heated to reflux for 6 hours and the water was collected by a moisture trap. The reaction mixture was extracted with 200 ml of 0.5% HCl in water. The aqueous layer was basified with NaHCO3 and extracted with CHCl3. Evaporation of the CHCl3 gave an oily residue which after chromotography on a column (silica gel/Et2O:EtOH=5:1) gave 1 g (23%) of white solid: m.p. 79.5°-82.5° C. The NMR, IR and mass spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C21H27O6N. the reaction The reaction mixture was heated to reflux for 6 hours the water was collected by a moisture trap The reaction mixture was extracted with 200 ml of 0.5% HCl in water extracted with CHCl3 Evaporation of the CHCl3 gave an oily residue which after chromotography on a column (silica gel/Et2O:EtOH=5:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Five milliliters of a methanol solution containing 0.6 g (16.0 mmol) of NaBH4 is added dropwise to 10 ml of a methanol solution containing 2.0 g (14 7 mmol) of 2-methoxybenzaldehyde, followed by stirring at room temperature for about 1 hour. After the progress of reaction has been confirmed by thin-layer chromatography, 100 ml of water is poured into the reaction solution to decompose excess NaBH4, followed by extraction with three 30 ml portions of ether. The ether layer is dried over anhydrous Na2SO4, and then filtered. When the solvent is removed by distillation, 1.95 g (yield: 96.1%) of 2-methoxybenzyl alcohol is obtained as an oily colorless product. After the progress of reaction is poured into the reaction solution followed by extraction with three 30 ml portions of ether The ether layer is dried over anhydrous Na2SO4 filtered When the solvent is removed by distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Five milliliters of a methanol solution containing 0.6 g (16.0 mmol) of NaBH4 is added dropwise to 10 ml of a methanol solution containing 2.0 g (14 7 mmol) of 2-methoxybenzaldehyde, followed by stirring at room temperature for about 1 hour. After the progress of reaction has been confirmed by thin-layer chromatography, 100 ml of water is poured into the reaction solution to decompose excess NaBH4, followed by extraction with three 30 ml portions of ether. The ether layer is dried over anhydrous Na2SO4, and then filtered. When the solvent is removed by distillation, 1.95 g (yield: 96.1%) of 2-methoxybenzyl alcohol is obtained as an oily colorless product. After the progress of reaction is poured into the reaction solution followed by extraction with three 30 ml portions of ether The ether layer is dried over anhydrous Na2SO4 filtered When the solvent is removed by distillation

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A test tube was charged with CuI (20 mg, 0.10 mmol, 10 mol %), 1,10-phenanthroline (36 mg, 0.20 mmol, 20 mol %), Cs2CO3 (456 mg, 1.4 mmol), 2-iodobenzylalcohol (234 mg, 1.0 mmol) and methanol (1.0 mL). The test tube was sealed and the reaction mixture was stirred at 80° C. for 24 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether. The filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane/diethyl ether 2:1) provided 122 mg (88% yield) of the title compound as a colorless oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane/diethyl ether 2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.200 g (0.6 mmol) of (3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid, 0.138 g (1.0 mmol) of 2-methoxybenzyl alcohol, 0.088 g (0.33 mmol) of CAS, 0.227 g (1.2 mmol) of DCC and 0.04 g (0.33 mmol) of DMAP were dissolved in 15 mL of CH2Cl2. The mixture was stirred for 24 h at room temperature. The solid was filtrated and the solvent was evaporated. The residual was dissolved in a suitable amount of ethyl acetate (20 ml) and then the mixture was filtered to remove insoluble substance. The ethyl acetate was added to 60 ml and then the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution and dried over Na2SO4. After the drying agent was removed and part of ethyl acetate was evaporated, the crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:6) to obtain the product as a oil (0.19 g). The solid was filtrated the solvent was evaporated The residual was dissolved in a suitable amount of ethyl acetate (20 ml) the mixture was filtered to remove insoluble substance The ethyl acetate was added to 60 ml the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution dried over Na2SO4 After the drying agent was removed part of ethyl acetate was evaporated the crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:6)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.200 g (0.6 mmol) of (3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid, 0.138 g (1.0 mmol) of 2-methoxybenzyl alcohol, 0.088 g (0.33 mmol) of CAS, 0.227 g (1.2 mmol) of DCC and 0.04 g (0.33 mmol) of DMAP were dissolved in 15 mL of CH2Cl2. The mixture was stirred for 24 h at room temperature. The solid was filtrated and the solvent was evaporated. The residual was dissolved in a suitable amount of ethyl acetate (20 ml) and then the mixture was filtered to remove insoluble substance. The ethyl acetate was added to 60 ml and then the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution and dried over Na2SO4. After the drying agent was removed and part of ethyl acetate was evaporated, the crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:6) to obtain the product as a oil (0.19 g). The solid was filtrated the solvent was evaporated The residual was dissolved in a suitable amount of ethyl acetate (20 ml) the mixture was filtered to remove insoluble substance The ethyl acetate was added to 60 ml the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution dried over Na2SO4 After the drying agent was removed part of ethyl acetate was evaporated the crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:6)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-hydroxymethyl-2-methoxybenzene (28.7 gram, 0.207 mol) in CH2Cl2 (574 ml) at 0° C. under nitrogen was added slowly PBr3 (13.66 ml, 0.145 mol). After stirring for an additional 1.5 hours, MeOH (13.66 ml) was added and stirred for 5 minutes. To this mixture was added dropwise 10% Na2CO3 (2 ml) solution and stirred for 5 minutes. The mixture was then washed with 10% Na2 CO3 (50 ml, 2×) and brine (100 ml). It was dried over MgSO4, and filtered. The filtrate was removed under vacuum to give an oil (40 gram) of 1-bromomethyl-2-methoxy-benzene. This material was used without purification. stirred for 5 minutes stirred for 5 minutes The mixture was then washed with 10% Na2 CO3 (50 ml, 2×) and brine (100 ml) It was dried over MgSO4 filtered The filtrate was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (148 mg, yield 100%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 10 min with heating under reflux for 3 hr the reaction the reaction solution was then extracted with chloroform by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order The extract was dried over sodium sulfate was then concentrated The residue was purified on a column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 93%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 10 min with heating under reflux for 3 hr the reaction the reaction solution was then extracted with chloroform by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order The extract was dried over sodium sulfate was then concentrated The residue was purified on a column