2-fluoro-5-methoxyphenol

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

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer , an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 ×5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer , an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL The mixture was heated to 150° C. the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer , an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 ×5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer , an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL The mixture was heated to 150° C. the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer , an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 ×5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer , an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL The mixture was heated to 150° C. the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3°-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 x5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer cooled to 3°-5° C When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3°-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 x5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer cooled to 3°-5° C When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)

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

Procedure: To a flask, 2-fluoro-5-methoxyphenol (6.00 g, 42 mmol), triethylamine (5.77 g, 57 mmol), and tetrahydrofuran (36.0 mL) were added, and the resulting mixture was cooled in an ice water bath under nitrogen atmosphere. To the solution, a solution of tert-butyldimethylsilyl chloride (6.89 g, 44 mmol) in tetrahydrofuran (30.0 mL) was added dropwise, and the resulting mixture was stirred overnight at room temperature. To the reaction mixture, heptane and a 2 N aqueous sodium hydroxide solution were added, and the resulting mixture was extracted. The organic layer was washed with water, and concentrated under reduced pressure to obtain the captioned compound (10.2 g) as a light brownish-red oil. the resulting mixture was cooled in an ice water bath under nitrogen atmosphere the resulting mixture was extracted The organic layer was washed with water concentrated under reduced pressure

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flask, 4-fluoroanisole (20.00 g, 159 mmol), N,N,N′,N″,N″-pentamethyldiethylenetriamine (27.75 g, 160 mmol), and tetrahydrofuran (100 mL) were added, and the resulting mixture was cooled to −70° C. under nitrogen atmosphere. To the solution, n-butyllithium (59.2 mL, 163 mmol, 2.76 M, in hexane) was added dropwise, and trimethyl borate (39.8 mL, 357 mmol) was added three hours later. One hour later, the reaction mixture was warmed to −10° C., and acetic acid (28.0 mL) was added thereto. The reaction temperature was then changed to 5° C., and 30% aqueous hydrogen peroxide solution (30 mL) was added dropwise to the reaction mixture, after which the resulting mixture was stirred overnight at room temperature. To the reaction mixture, 10% aqueous sodium sulfite solution was added, and the resulting mixture was extracted with tert-butyl methyl ether. To the organic layer, a 2 N aqueous sodium hydroxide solution was added, and the resulting mixture was extracted. After adding 5 N hydrochloric acid to the aqueous layer to adjust the pH to 6, the resulting mixture was extracted with tert-butyl methyl ether. The organic layer was sequentially washed with water and 5% saline, dried over anhydrous magnesium sulfate, and then filtered. The filtrate obtained was concentrated under reduced pressure to obtain the captioned compound (21.7 g) as a colorless oil. One hour later, the reaction mixture was warmed to −10° C. was then changed to 5° C. the resulting mixture was extracted with tert-butyl methyl ether To the organic layer, a 2 N aqueous sodium hydroxide solution was added the resulting mixture was extracted After adding 5 N hydrochloric acid to the aqueous layer the resulting mixture was extracted with tert-butyl methyl ether The organic layer was sequentially washed with water and 5% saline dried over anhydrous magnesium sulfate filtered The filtrate obtained was concentrated under reduced pressure

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

Procedure: To a 200 ml THF solution containing 50.1 g of 1-fluoro-4-methoxybenzene and 70g of N,N,N′,N′,N″-pentamethyldiethylenetriamine there was added dropwise 150 ml of n-butyllithium (2.66 M, hexane solution) over a period of 30 minutes, at −74° C. under a nitrogen atmosphere. After stirring for 3 hours at between −74° C. and −70° C., 100 ml of trimethyl borate was added. The temperature of the reaction mixture was then slowly raised to room temperature. Next, 70 ml of acetic acid and 75 ml of 30% aqueous hydrogen peroxide were added, and the reaction mixture was stirred overnight at room temperature. Water was then added to the reaction mixture, and then it was extracted with a mixture of hexane and ethyl acetate and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, and the filtrate was concentrated under reduced pressure to give a crude product of 1-fluoro-2-hydroxy-4-methoxybenzene (65.59 g) as a white solid. at −74° C. the reaction mixture was stirred overnight at room temperature it was extracted with a mixture of hexane and ethyl acetate dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure

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

Procedure: To a 200 ml THF solution containing 50.1 g of 1-fluoro-4-methoxybenzene and 70 g of N,N,N′,N′,N″-pentamethyldiethylenetriamine there was added dropwise 150 ml of n-butyllithium (2.66 M, hexane solution) over a period of 30 minutes, at −74° C. under a nitrogen atmosphere. After stirring for 3 hours at between −74° C. and −70° C., 100 ml of trimethyl borate was added. The temperature of the reaction mixture was then slowly raised to room temperature. Next, 70 ml of acetic acid and 75 ml of 30% aqueous hydrogen peroxide were added, and the reaction mixture was stirred overnight at room temperature. Water was then added to the reaction mixture, and then it was extracted with a mixture of hexane and ethyl acetate and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, and the filtrate was concentrated under reduced pressure to give a crude product of 1-fluoro-2-hydroxy-4-methoxybenzene (65.59 g) as a white solid. at −74° C. the reaction mixture was stirred overnight at room temperature it was extracted with a mixture of hexane and ethyl acetate dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3°-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 ×5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer cooled to 3°-5° C When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The method used to prepare the phenol is basically the procedure reported by Claudi et. al. [med. Chem. 33, 2408-2412 (1990) with modification according to Lambooy [J. Amer. Chem. Soc. 72, 5327-5328 (1950)]. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer, 2-fluoro-methoxyaniline (11.3 g, 80 mmol ), concentrated sulfuric acid (35 mL) and water (200 mL) were mixed and then cooled to 3°-5° C. A solution of sodium nitrite (6.07 g; 88 mmol) in water (20 mL) was added dropwise to the stirred mixture above at 2°-4° C. When the addition was completed the solution was stirred for five minutes and then urea (0.48 g) was added followed by water (100 mL). Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL dropping funnel was attached. In the flask CuSO4 ×5H2O (56 g), concentrated sulfuric acid (160 mL) and water (160 mL) were placed. The mixture was heated to 150° C., the diazonium salt solution, cooled all the time by adding small chunks of the ice to it, was added dropwise from the dropping funnel, and a current of steam was passed through the system to remove the phenol. The distillate was extracted with ether (3×400 mL) and the combined ether extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85) to afford 4.03 g of the title compound as a crystalline solid. Mp. 25°-26° C. In a three-necked round-bottom flask (1000 mL), equipped with dropping-funnel and a magnetic stirrer cooled to 3°-5° C When the addition Meanwhile an apparatus was prepared consisting of a three-necked round-bottom flask (1000 mL), a thermometer, an electrical heating mantle, a steam distillation apparatus, and long (40 cm) water-jacketed condensor on top of which a 500 mL the diazonium salt solution, cooled all the time by adding small chunks of the ice to it was added dropwise from the dropping funnel to remove the phenol The distillate was extracted with ether (3×400 mL) the combined ether extracts were dried (MgSO4) filtered concentrated in vacuo The crude phenol was purified on a silica column eluted with ether/n-hexane (15:85)