1-bromonaphthalen-2-ol

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

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

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

Procedure: To a suspension of 1-bromo-2-naphthol (15.0 g, 67.3 mmol) and K2CO3 (18.6 g, 135 mmol) in DMF (100 mL) was added benzyl bromide (9.6 mL, 81 mmol) and the mixture was stirred at 60° C. for 5 h. After cooling to room temperature, the solvent was evaporated in vacuo and the residue, dissolved in a small amount of CH2Cl2, passed through a thin pad of flash silica. Fractions containing the product were evaporated in vacuo to give an off-white solid. Crystallisation from CH2Cl2/petrol gave the title compound, 1-bromo-2-(phenylmethoxy)naphthalene, as a white crystalline solid (16.0 g, 76%). The mother liquor was concentrated and purified by flash chromatography (petrol/CH2Cl2, 2/1) to give an additional amount of the product (3.7 g, 17%; total yield: 93%). Rf =0.50 (petrol/CH2Cl2, 2/1); mp 104-106° C. (CH2Cl2/petrol); 1H NMR (250 MHz, CDCl3) δ5.35 (s, 2H), 7.32 (d, J=9.0 Hz, 1H), 7.38-7.50 (m, 4H), 7.57-7.66 (m, 2H), 7.79-7.86 (m, 3H), and 8.31 (d, J=8.5 Hz, 1H); 13C NMR (63 MHz, CDCl3) δ71.81, 110.0, 115.6, 124.6, 126.3, 127.2, 127.8, 128.1 (2C), 128.7, 128.9, 130.1, 133.2, 136.7 and 153.0; IR (CHCl3) νmax 1626, 1596, 1502, 1350, and 1268 cm−1; MS (EI+) m/z (rel intensity) 314/312 (25%, M+) and 91 (100); HRMS calcd for C17H13BrO (M+) 312.0150, found 312.0150. Anal. Calcd for C17H13BrO: C, 65.19; H, 4.18; Br, 25.51. Found: C, 64.94; H, 4.12; Br, 25.71. After cooling to room temperature the solvent was evaporated in vacuo the residue, dissolved in a small amount of CH2Cl2 Fractions containing the product were evaporated in vacuo to give an off-white solid Crystallisation from CH2Cl2/petrol

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

Procedure: A suspension containing 22.3 g of 1-bromonaphth-2-ol, 27.75 g of 1-chloro-2,3-epoxypropane and 27.6 g of potassium carbonate in 200 ml of butanone is refluxed overnight. The inorganic salts are filtered off and drained and the filtrate is then evaporated under vacuum. The oil obtained is distilled under 0.01 mm of mercury. is refluxed overnight The inorganic salts are filtered off the filtrate is then evaporated under vacuum The oil obtained is distilled under 0.01 mm of mercury

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

Procedure: A 500 mL three-necked round-bottomed flask was charged with 1-bromonaphthalen-2-ol (30.0 g, 134.5 mmol), potassium hydroxide (KOH) (11.3 g, 201.7 mmol) and DMSO (300 mL), and the mixture was stirred under nitrogen atmosphere for 10 minutes, After cooling the mixture by using ice-water bath, iodomethane (28.6 g, 201.7 mmol) was slowly added dropwise thereto. Then, the resultant mixture was stirred under nitrogen atmosphere at ambient temperature for 12 hours, and then at 50° C. for 1 hour. After cooling to ambient temperature, the reaction mixture was mixed with water (500 mL), and extracted with diethyl ether. Organic mixture was washed three times with distilled water, and dried over anhydrous magnesium sulfate (MgSO4). After removing the solvent by using a rotary evaporator, the residue was purified via silica gel column chromatography (eluent: n-hexane) to obtain 1-bromo-2-methoxynaphthalene (22.0 g, yield: 69.0%) as white solid. After cooling the mixture at 50° C. for 1 hour extracted with diethyl ether Organic mixture was washed three times with distilled water dried over anhydrous magnesium sulfate (MgSO4) After removing the solvent a rotary evaporator the residue was purified via silica gel column chromatography (eluent: n-hexane)

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

Procedure: To a suspension of 1-bromo-2-naphthol (15.0 g, 67.3 mmol) and K2CO3 (18.6 g, 135 mmol) in DMF (100 mL) was added benzyl bromide (9.6 mL, 81 mmol) and the mixture was stirred at 60° C. for 5 h. After cooling to room temperature, the solvent was evaporated in vacuo and the residue, dissolved in a small amount of CH2Cl2, passed through a thin pad of flash silica. Fractions containing the product were evaporated in vacuo to give an off-white solid. Crystallisation from CH2Cl2/petrol gave the title compound, 1-bromo-2-(phenylmethoxy)naphthalene, as a white crystalline solid (16.0 g, 76%). The mother liquor was concentrated and purified by flash chromatography (petrol/CH2Cl2, 2/1) to give an additional amount of the product (3.7 g, 17%; total yield: 93%). Rf =0.50 (petrol/CH2Cl2, 2/1); mp 104-106° C. (CH2Cl2/petrol); 1H NMR (250 MHz, CDCl3) δ5.35 (s, 2H), 7.32 (d, J=9.0 Hz, 1H), 7.38-7.50 (m, 4H), 7.57-7.66 (m, 2H), 7.79-7.86 (m, 3H), and 8.31 (d, J=8.5 Hz, 1H); 13C NMR (63 MHz, CDCl3) δ71.81, 110.0, 115.6, 124.6, 126.3, 127.2, 127.8, 128.1 (2C), 128.7, 128.9, 130.1, 133.2, 136.7 and 153.0; IR (CHCl3) νmax 1626, 1596, 1502, 1350, and 1268 cm−1; MS (EI+) m/z (rel intensity) 314/312 (25%, M+) and 91 (100); HRMS calcd for C17H13BrO (M+) 312.0150, found 312.0150. Anal. Calcd for C17H13BrO: C, 65.19; H, 4.18; Br, 25.51. Found: C, 64.94; H, 4.12; Br, 25.71. After cooling to room temperature the solvent was evaporated in vacuo the residue, dissolved in a small amount of CH2Cl2 Fractions containing the product were evaporated in vacuo to give an off-white solid Crystallisation from CH2Cl2/petrol

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

Procedure: To a suspension of 1-bromo-2-naphthol (15.0 g, 67.3 mmol) and K2CO3 (18.6 g, 135 mmol) in DMF (100 mL) was added benzyl bromide (9.6 mL, 81 mmol) and the mixture was stirred at 60° C. for 5 h. After cooling to room temperature, the solvent was evaporated in vacuo and the residue, dissolved in a small amount of CH2Cl2, passed through a thin pad of flash silica. Fractions containing the product were evaporated in vacuo to give an off-white solid. Crystallisation from CH2Cl2/petrol gave the title compound, 1-bromo-2-(phenylmethoxy)naphthalene, as a white crystalline solid (16.0 g, 76%). The mother liquor was concentrated and purified by flash chromatography (petrol/CH2Cl2, 2/1) to give an additional amount of the product (3.7 g, 17%; total yield: 93%). Rf =0.50 (petrol/CH2Cl2, 2/1); mp 104-106° C. (CH2Cl2/petrol); 1H NMR (250 MHz, CDCl3) δ5.35 (s, 2H), 7.32 (d, J=9.0 Hz, 1H), 7.38-7.50 (m, 4H), 7.57-7.66 (m, 2H), 7.79-7.86 (m, 3H), and 8.31 (d, J=8.5 Hz, 1H); 13C NMR (63 MHz, CDCl3) δ71.81, 110.0, 115.6, 124.6, 126.3, 127.2, 127.8, 128.1 (2C), 128.7, 128.9, 130.1, 133.2, 136.7 and 153.0; IR (CHCl3) νmax 1626, 1596, 1502, 1350, and 1268 cm−1; MS (EI+) m/z (rel intensity) 314/312 (25%, M+) and 91 (100); HRMS calcd for C17H13BrO (M+) 312.0150, found 312.0150. Anal. Calcd for C17H13BrO: C, 65.19; H, 4.18; Br, 25.51. Found: C, 64.94; H, 4.12; Br, 25.71. After cooling to room temperature the solvent was evaporated in vacuo the residue, dissolved in a small amount of CH2Cl2 Fractions containing the product were evaporated in vacuo to give an off-white solid Crystallisation from CH2Cl2/petrol

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

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

Procedure: In a 200-mL three-neck flask were put 5.8 g (26 mmol) of 1-bromo-2-naphthol, 4.5 g (26 mmol) of 3-chloro-2-fluorobenzeneboronic acid, and 0.40 g (1.3 mmol) of tri(ortho-tolyl)phosphine, and the air in the flask was replaced with nitrogen. To this mixture, 150 mL of toluene, 50 mL of ethanol, and 21 mL of an aqueous solution of potassium carbonate (2.0 mol/L) were added. The mixture was degassed by being stirred while the pressure in the flask was reduced; then, the air in the flask was replaced with nitrogen. To this mixture was added 58 mg (0.26 mmol) of palladium(II)acetate, and the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours. After stirring, the organic layer of the mixture was washed with water and the aqueous layer was subjected to extraction with toluene. The solution of the extract combined with the organic layer was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over magnesium sulfate. The resulting mixture was gravity-filtered, and the resulting filtrate was concentrated to give a brown liquid. The liquid was purified by silica gel column chromatography using a mixed solvent (toluene: hexane=9:1) as a developing solvent, so that 3.1 g of a brown liquid of a target substance was produced in a yield of 44%. In a 200-mL three-neck flask were put The mixture was degassed the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours After stirring the organic layer of the mixture was washed with water the aqueous layer was subjected to extraction with toluene was washed with a saturated aqueous solution of sodium chloride the organic layer was dried over magnesium sulfate The resulting mixture was gravity-filtered the resulting filtrate was concentrated to give a brown liquid The liquid was purified by silica gel column chromatography

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

Procedure: In a 200-mL three-neck flask were put 5.8 g (26 mmol) of 1-bromo-2-naphthol, 4.5 g (26 mmol) of 3-chloro-2-fluorobenzeneboronic acid, and 0.40 g (1.3 mmol) of tri(ortho-tolyl)phosphine, and the air in the flask was replaced with nitrogen. To this mixture, 150 mL of toluene, 50 mL of ethanol, and 21 mL of an aqueous solution of potassium carbonate (2.0 mol/L) were added. The mixture was degassed by being stirred while the pressure in the flask was reduced; then, the air in the flask was replaced with nitrogen. To this mixture was added 58 mg (0.26 mmol) of palladium(II)acetate, and the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours. After stirring, the organic layer of the mixture was washed with water and the aqueous layer was subjected to extraction with toluene. The solution of the extract combined with the organic layer was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over magnesium sulfate. The resulting mixture was gravity-filtered, and the resulting filtrate was concentrated to give a brown liquid. The liquid was purified by silica gel column chromatography using a mixed solvent (toluene: hexane=9:1) as a developing solvent, so that 3.1 g of a brown liquid of a target substance was produced in a yield of 44%. In a 200-mL three-neck flask were put The mixture was degassed the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours After stirring the organic layer of the mixture was washed with water the aqueous layer was subjected to extraction with toluene was washed with a saturated aqueous solution of sodium chloride the organic layer was dried over magnesium sulfate The resulting mixture was gravity-filtered the resulting filtrate was concentrated to give a brown liquid The liquid was purified by silica gel column chromatography

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

Procedure: In a 200-mL three-neck flask were put 5.8 g (26 mmol) of 1-bromo-2-naphthol, 4.5 g (26 mmol) of 3-chloro-2-fluorobenzeneboronic acid, and 0.40 g (1.3 mmol) of tri(ortho-tolyl)phosphine, and the air in the flask was replaced with nitrogen. To this mixture, 150 mL of toluene, 50 mL of ethanol, and 21 mL of an aqueous solution of potassium carbonate (2.0 mol/L) were added. The mixture was degassed by being stirred while the pressure in the flask was reduced; then, the air in the flask was replaced with nitrogen. To this mixture was added 58 mg (0.26 mmol) of palladium(II)acetate, and the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours. After stirring, the organic layer of the mixture was washed with water and the aqueous layer was subjected to extraction with toluene. The solution of the extract combined with the organic layer was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over magnesium sulfate. The resulting mixture was gravity-filtered, and the resulting filtrate was concentrated to give a brown liquid. The liquid was purified by silica gel column chromatography using a mixed solvent (toluene: hexane=9:1) as a developing solvent, so that 3.1 g of a brown liquid of a target substance was produced in a yield of 44%. In a 200-mL three-neck flask were put The mixture was degassed the resulting mixture was stirred at 90° C. under a nitrogen stream for 7 hours After stirring the organic layer of the mixture was washed with water the aqueous layer was subjected to extraction with toluene was washed with a saturated aqueous solution of sodium chloride the organic layer was dried over magnesium sulfate The resulting mixture was gravity-filtered the resulting filtrate was concentrated to give a brown liquid The liquid was purified by silica gel column chromatography

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

Procedure: 1-Bromo-2-naphthol (2.0 g, 8.97 mmol) was dissolved in THF (20 mL), and the solution was cooled to 0 deg in an ice bath. NaH was added thereto (60% dispersion of in mineral oil, 430 mg 10.8 mmol), followed by MeI (1.2 mL, 19.6 mmol) as bubbling subsided. The reaction mixture was heated to reflux overnight, cooled to room temperature, and water added dropwise thereto until bubbling subsided. The reaction mixture was diluted with EtOAc, and the organic layer was washed once each with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 10% to 50% EtOAc/hexanes to afford 1-bromo-2-methoxynaphthalene as a solid. LC/MS (ES MS, M+H+ found: 238) and proton NMR (400 MHz, CDCl3) δ 4.04 (s, 3H), 7.28 (d, J=9 Hz, 1H), 7.42 (t, J=7 Hz, 1H), 7.58 (t, J=6.8 Hz, 1H), 7.8 (dd, J=9 Hz, 2H), 8.2 (d, J=8.6 Hz, 1H). the solution was cooled to 0 deg in an ice bath as bubbling The reaction mixture was heated to reflux overnight water added dropwise until bubbling The reaction mixture was diluted with EtOAc the organic layer was washed once each with water and brine dried over sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with 10% to 50% EtOAc/hexanes