5-chloro-2-iodophenol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.60000002384185791; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromo-pyridin-2-yl)-methanol (7.39 g, 39.30 mmoles), and triethylamine (7.15 mL, 51.3 mmoles) are combined in tetrahydrofuran (70 mL) under nitrogen. The solution is chilled to 0.6° C. with an ice bath. Methanesulfonyl chloride (3.35 mL, 43.28 mmol) is added dropwise over 20 min, controlling the exotherm such that the internal temperature does not exceed 5° C. Following the addition, the reaction is stirred over an ice bath. After 20 min HPLC analysis shows that the (3-Bromo-pyridin-2-yl)-methanol is fully consumed. Triethylamine hydrochloride is filtered using a fitted glass funnel, washing with cold THF (50 mL). The THF filtrate containing the mesylate is placed under nitrogen and chilled in an ice bath. 2-Iodo-5-chlorophenol (10.00 g, 39.30 mmoles) is added, followed by addition of sodium t-butoxide (4.10 g, 41.38 mmol) in two equal portions with a mild exotherm of about 5° C. for each addition. The ice bath is removed and the reaction allowed to stir overnight. The reaction is quenched with water (50 mL) and the lower aqueous layer allowed to slowly separate. The organic portion is washed with brine (25 mL), and then the brine and aqueous portions back-extracted with THF (10 mL). The organic portions are combined and dried over sodium sulfate, filtered, and concentrated to afford a rusty orange solid. The solid is dissolved in dichloromethane (25 mL) and chromatographed on an AnaLogix Inc., Intelliflash 180 automated chromatography instrument, version 1.8.0. using a gradient of 10- 20% ethyl acetate/hexanes over 35 min to afford 11.0 g (65%) of the product as a yellow solid. 1H NMR (DMSO) δ 5.31 (2H, s), 6.85 (1H, dd), 7.25 (1H, m), 7.39 (1H, dd), 7.77 (1H, d), 8.17 (1H, d), 8.59 (1H, d). does not exceed 5° C the addition is fully consumed Triethylamine hydrochloride is filtered washing with cold THF (50 mL) The THF filtrate containing the mesylate chilled in an ice bath The ice bath is removed to stir overnight The reaction is quenched with water (50 mL) to slowly separate The organic portion is washed with brine (25 mL) the brine and aqueous portions back-extracted with THF (10 mL) dried over sodium sulfate filtered concentrated to afford a rusty orange solid chromatographed on an AnaLogix Inc over 35 min

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromo-pyridin-2-yl)-methanol (3.4 g, 18 mmol), and 2-iodo-5-chlorophenol 4.5 g, 18 mmol), are dissolved in benzene (60 mL) and cooled to 0° C. To the solution is added tributylphosphine (15 mL, 90 mmol), and 1,1′-(azodicarbonyl) dipiperidine (ADDP) (6.6 g, 18 mmol) and the mixture is heated at 40° C. for 3 h. The reaction mixture is diluted with ethyl acetate, washed with saturated aqueous NH4Cl and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane) to yield 3.77 g (51%) of the title compound as a white solid. GCMS m/e 296, 298 [M-I]−. the mixture is heated at 40° C. for 3 h washed with saturated aqueous NH4Cl and brine dried over MgSO4 filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Amino-5-chlorophenol (5.7 g, 40 mmol) is dissolved in DMSO/water/H2SO4 (200/60/140 mL) and cooled to 0° C. To this solution is added sodium nitrite (4.1 g, 60 mmol) in water (20 mL) and the mixture is stirred for 1 h at 0° C. To the mixture is added potassium iodide (19.9 g, 120 mmol) in water (20 mL) and the mixture is stirred at room temperature for 1 h. Another batch of potassium iodide (19.9 g, 120 mmol) in water (20 mL) is added and the mixture is stirred at room temperature for 1 h. The mixture is diluted with ethyl acetate, washed with water, saturated aqueous sodium sulfate, and brine. The organic portion is dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage™ Si65M, 20% ethyl acetate/hexane) to yield 8.09 g (79%) of the title compound as a pink solid. GCMS m/e 254 [M]−. the mixture is stirred at room temperature for 1 h the mixture is stirred at room temperature for 1 h washed with water, saturated aqueous sodium sulfate, and brine The organic portion is dried over MgSO4 filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (Biotage™ Si65M, 20% ethyl acetate/hexane)

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

実験手順: A mixture of 5-chloro-2-iodophenol (4.95 g), methyl bromoacetate (1.85 ml) and potassium carbonate (2.79 g) in acetonitrile (20 ml) was heated under reflux for 2 h. Aq HCl was added and the mixture was extracted with ether (three times). The organic extracts were dried (MgSO4), evaporated and purified by chromatography (silica, petrol-ether as eluent) to give the sub-title compound (5.75 g). was heated under reflux for 2 h the mixture was extracted with ether (three times) The organic extracts were dried (MgSO4) evaporated purified by chromatography (silica, petrol-ether as eluent)

反応条件: temp:0.60000002384185791; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromo-pyridin-2-yl)-methanol (7.39 g, 39.30 mmoles), and triethylamine (7.15 mL, 51.3 mmoles) are combined in tetrahydrofuran (70 mL) under nitrogen. The solution is chilled to 0.6° C. with an ice bath. Methanesulfonyl chloride (3.35 mL, 43.28 mmol) is added dropwise over 20 min, controlling the exotherm such that the internal temperature does not exceed 5° C. Following the addition, the reaction is stirred over an ice bath. After 20 min HPLC analysis shows that the (3-Bromo-pyridin-2-yl)-methanol is fully consumed. Triethylamine hydrochloride is filtered using a fitted glass funnel, washing with cold THF (50 mL). The THF filtrate containing the mesylate is placed under nitrogen and chilled in an ice bath. 2-Iodo-5-chlorophenol (10.00 g, 39.30 mmoles) is added, followed by addition of sodium t-butoxide (4.10 g, 41.38 mmol) in two equal portions with a mild exotherm of about 5° C. for each addition. The ice bath is removed and the reaction allowed to stir overnight. The reaction is quenched with water (50 mL) and the lower aqueous layer allowed to slowly separate. The organic portion is washed with brine (25 mL), and then the brine and aqueous portions back-extracted with THF (10 mL). The organic portions are combined and dried over sodium sulfate, filtered, and concentrated to afford a rusty orange solid. The solid is dissolved in dichloromethane (25 mL) and chromatographed on an AnaLogix Inc., Intelliflash 180 automated chromatography instrument, version 1.8.0. using a gradient of 10- 20% ethyl acetate/hexanes over 35 min to afford 11.0 g (65%) of the product as a yellow solid. 1H NMR (DMSO) δ 5.31 (2H, s), 6.85 (1H, dd), 7.25 (1H, m), 7.39 (1H, dd), 7.77 (1H, d), 8.17 (1H, d), 8.59 (1H, d). does not exceed 5° C the addition is fully consumed Triethylamine hydrochloride is filtered washing with cold THF (50 mL) The THF filtrate containing the mesylate chilled in an ice bath The ice bath is removed to stir overnight The reaction is quenched with water (50 mL) to slowly separate The organic portion is washed with brine (25 mL) the brine and aqueous portions back-extracted with THF (10 mL) dried over sodium sulfate filtered concentrated to afford a rusty orange solid chromatographed on an AnaLogix Inc over 35 min

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromo-pyridin-2-yl)-methanol (3.4 g, 18 mmol), and 2-iodo-5-chlorophenol 4.5 g, 18 mmol), are dissolved in benzene (60 mL) and cooled to 0° C. To the solution is added tributylphosphine (15 mL, 90 mmol), and 1,1′-(azodicarbonyl) dipiperidine (ADDP) (6.6 g, 18 mmol) and the mixture is heated at 40° C. for 3 h. The reaction mixture is diluted with ethyl acetate, washed with saturated aqueous NH4Cl and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane) to yield 3.77 g (51%) of the title compound as a white solid. GCMS m/e 296, 298 [M-I]−. the mixture is heated at 40° C. for 3 h washed with saturated aqueous NH4Cl and brine dried over MgSO4 filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromo-pyridin-2-yl)-methanol (3.4 g, 18 mmol), and 2-iodo-5-chlorophenol 4.5 g, 18 mmol), are dissolved in benzene (60 mL) and cooled to 0° C. To the solution is added tributylphosphine (15 mL, 90 mmol), and 1,1′-(azodicarbonyl) dipiperidine (ADDP) (6.6 g, 18 mmol) and the mixture is heated at 40° C. for 3 h. The reaction mixture is diluted with ethyl acetate, washed with saturated aqueous NH4Cl and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane) to yield 3.77 g (51%) of the title compound as a white solid. GCMS m/e 296, 298 [M-I]−. the mixture is heated at 40° C. for 3 h washed with saturated aqueous NH4Cl and brine dried over MgSO4 filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Amino-5-chlorophenol (5.7 g, 40 mmol) is dissolved in DMSO/water/H2SO4 (200/60/140 mL) and cooled to 0° C. To this solution is added sodium nitrite (4.1 g, 60 mmol) in water (20 mL) and the mixture is stirred for 1 h at 0° C. To the mixture is added potassium iodide (19.9 g, 120 mmol) in water (20 mL) and the mixture is stirred at room temperature for 1 h. Another batch of potassium iodide (19.9 g, 120 mmol) in water (20 mL) is added and the mixture is stirred at room temperature for 1 h. The mixture is diluted with ethyl acetate, washed with water, saturated aqueous sodium sulfate, and brine. The organic portion is dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage™ Si65M, 20% ethyl acetate/hexane) to yield 8.09 g (79%) of the title compound as a pink solid. GCMS m/e 254 [M]−. the mixture is stirred at room temperature for 1 h the mixture is stirred at room temperature for 1 h washed with water, saturated aqueous sodium sulfate, and brine The organic portion is dried over MgSO4 filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (Biotage™ Si65M, 20% ethyl acetate/hexane)

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

実験手順: A mixture of 5-chloro-2-iodophenol (4.95 g), methyl bromoacetate (1.85 ml) and potassium carbonate (2.79 g) in acetonitrile (20 ml) was heated under reflux for 2 h. Aq HCl was added and the mixture was extracted with ether (three times). The organic extracts were dried (MgSO4), evaporated and purified by chromatography (silica, petrol ether as eluent) to give the sub-title compound (5.75 g). was heated under reflux for 2 h the mixture was extracted with ether (three times) The organic extracts were dried (MgSO4) evaporated purified by chromatography (silica, petrol ether as eluent)

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: A mixture of 5-chloro-2-iodophenol (4.95 g), methyl bromoacetate (1.85 ml) and potassium carbonate (2.79 g) in acetonitrile (20 ml) was heated under reflux for 2 h. Aq HCl was added and the mixture was extracted with ether (three times). The organic extracts were dried (MgSO4), evaporated and purified by chromatography (silica, petrol ether as eluent) to give the sub-title compound (5.75 g). was heated under reflux for 2 h the mixture was extracted with ether (three times) The organic extracts were dried (MgSO4) evaporated purified by chromatography (silica, petrol ether as eluent)