| 70% |
With N-iodo-succinimide; In acetic acid; at 80℃; for 20.5h; |
8-Fluoro-3-iodoquinoline (D1) M-iodosuccinimide (8.1 g, 36. 0 mmol, 2 eq. ) was added to a solution of <strong>[394-68-3]8-fluoroquinoline</strong> (2. 65 g, 18.0 mmol) in AcOH (13.25 ml, 5 vol). The mixture was stirred and placed in an oil bath which was then heated to 80°C. After 20 hrs 25min the flask was removed from the oil bath and allowed to cool to room temperature. CH2CI2 (13.5 mi) was added, the solution was washed with 10percent w/v Na2SO3 (aq) (23.5 ml), then with H20 (13.5 ml) before being concentrated under reduced pressure. The crude product was pre-absorbed on silica and purified via column chromatography, eluting with 19: 1 isohexane/EtOAc 1percent Et3N to yield 8-fluoro-3-iodoquinoline (D1) as a white solid (3. 46 g, 12.7 mmol, 70percent). 'H NMR (CDC13, 400MHz) otilde; 7.40-7. 45 (1H, m, ArH), 7.50-7. 52 (2H, m, Art0, 8.58 (1H, t, J 1.7 Hz, ArM), 9.09 (1H, d, J 2. 0 Hz, Arm. |
| 70% |
With N-iodo-succinimide; acetic acid; at 80℃; for 20.4167h; |
Description 1; 8-Fluoro-3-iodoquinoline (D1); N-lodosuccinimide (8.1 g, 36.0 mmol, 2 eq. ) was added to a solution of <strong>[394-68-3]8-fluoroquinoline</strong> (2.65 g, 18.0 mmol) in AcOH (13.25 ml, 5 vol). The mixture was stirred and placed in an oil bath which was then heated to 80°C. After 20 hrs 25 min the flask was removed from the oil bath and allowed to cool to room temperature. Dichloromethane (13.5 ml) was added, the solution was washed with 10percent w/v Na2S03 (aq) (23.5 ml), then with H20 (13.5 ml) before being concentrated under reduced pressure. The crude product was pre- absorbed on silica and purified via column chromatography, eluting with 19:1 isohexane/EtOAc 1percent Et3N to yield 8-fluoro-3-iodoquinoline (D1) as a white solid (3.46 g, 12.7 mmol, 70percent). 1H NMR (CDCI3, 400M Hz) 8 7.40-7.45 (1 H, m, Arm, 7.50-7.52 (2H, m, ArH), 8.58 (1 H, t, J 1.7 Hz, Arm, 9.09 (1 H, d, J 2.0 Hz, ArH). |
| 66 - 75% |
With N-iodo-succinimide; In acetic acid; at 80℃; for 23.5 - 24h;Product distribution / selectivity; |
Example 1aPreparation of 8-fluoro-3-iodoquinolineN-lodosuccinamide (68.56 g, 305.81 mmol, 1.5 eq) was added to a solution of 8- fluoroquinoline (30 g, 203.87 mmol) in AcOH (129 ml, 4.3 vol). The mixture was stirred and heated to 800C, under N2 in a 250 mL CLR (Controlled Laboratory Reactor). After 24 hrs Na2SO3 (15 g, 0.5 weight) was added to the flask with H2O (63 ml, 2.1 vol) and the solution was stirred, whilst be maintained at 8O0C for 1 hour to quench the remaining iodine. After an hour the reaction was allowed to cool from 800C to 220C over 30 minutes. Once 220C had been reached the crystals were filtered off under vacuum and washed with 2:1 AcOH/H2O (60 ml, 2 vol) and H2O (180 mL, 3 x 2 vol) and the crystals were pulled dry. The crystals were dried in an oven which was connected to an oil bath at 5O0C under reduced pressure.The cake was removed from the oven to afford the title compound as a pale brown solid (38.63 g, 66percent).; Example 1bPreparation of 8-fluoro-3-iodoquinolineN-lodosuccinimide (NIS) (229.0 g, 1.018 mol, 2.29 wt, 1.50 eq) was added to a stirred solution of <strong>[394-68-3]8-fluoroquinoline</strong> (100.O g, 0.68 mol, 1.00 wt, 1.00 eq) in glacial acetic acid (AcOH) (430 ml, 4.3 vol). <strong>[394-68-3]8-Fluoroquinoline</strong> may be obtained from Orgasynth (www.orgasynth.com). The mixture was heated to circa 80°C under nitrogen. After 23.5 EPO <DP n="14"/>hr sodium sulphite (50.0 g, 0.397 mol, 0.50 wt. 0.584 eq) and water (210 ml, 2.1 vol) were added and the mixture reheated to circa 80cC. After 1.5 hr the mixture was allowed to cool to circa 60-650C and seeded with 8-fluoro-3-iodoquinoline (100 mg,0.1percent wt). The product soon crystallised and the stirred slurry was allowed to cool over1.5 hr to ambient temperature. After 1.25 hr the product was collected by vacuum filtration. The bed was washed with 1 :1 acetic acid / water (2 x 300 ml, 3 vol) and water(2 x 300 ml, 2 x 3 vol). The bed was pulled dry for 5 min and the material used without further processing.A sample of the material was dried in vacuo at 40-450C, to afford the desired product in75percent yield.1H NMR, D4 MeOH, 400 MHz7.50 ppm (1 H, ddd, J 1.5, 7.5 11.0 Hz), 7.58 ppm (1 H, dt, J 5 8 Hz), 7.64 ppm (1 H, dd, J 1.0 8.5 Hz), 8.78 ppm (1 H. t, J 1.5 Hz), 8.99 ppm (1 H, d, J 2.0 Hz) |
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