3-fluoro-2-iodoaniline;hydrochloride

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Iodo-3-fluoroaniline hydrochloride (5.7 g, 0.021 mol) was stirred in 7.4 mL of concentrated HCl and cooled to -10° C. An aqueous solution of sodium nitrite (1.63 g, 0.024 mL) in 5 mL water was added dropwise over a 20 minute period, stannous chloride (9.95 g, 0.044 mol) in 12 mL of 6N HCl added at -5° C., warmed to room temperature and stirring continued for 4 hours. The reaction mixture was cooled to 0° C., and made basic with 50% NaOH (pH 10-11), extracted with ether, washed with water, brine, dried (MgSO4), filtered and concentrated to give the hydrazine. Addition of ethereal HCl (pH 1-2) gave 4.6 g of the title compound, m.p. 165°-167° C. warmed to room temperature The reaction mixture was cooled to 0° C. extracted with ether washed with water, brine dried (MgSO4) filtered concentrated

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Iodo-3-fluoroaniline hydrochloride (5.7 g, 0.021 mol) was stirred in 7.4 mL of concentrated HCl and cooled to -10° C. An aqueous solution of sodium nitrite (1.63 g, 0.024 mL) in 5 mL water was added dropwise over a 20 minute period, stannous chloride (9.95 g, 0.044 mol) in 12 mL of 6N HCl added at -5° C., warmed to room temperature and stirring continued for 4 hours. The reaction mixture was cooled to 0° C., and made basic with 50% NaOH (pH 10-11), extracted with ether, washed with water, brine, dried (MgSO4), filtered and concentrated to give the hydrazine. Addition of ethereal HCl (pH 1-2) gave 4.6 g of the title compound, m.p. 165°-167° C. warmed to room temperature The reaction mixture was cooled to 0° C. extracted with ether washed with water, brine dried (MgSO4) filtered concentrated

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

実験手順: A solution of 2-iodo-3-fluoronitrobenzene (27.0 g, 0.101 mol) in tetrahydrofuran (200 mL) was added dropwise over a 10 minute period to a stirring solution of stannous chloride dihydrate (68.0 g, 0.302 mol) in concentrated hydrochloric acid (200 mL). After 3 hours at room temperature the reaction was poured onto ice, made alkaline (pH 11) with 50% NaOH, and extracted with diethyl ether. The combined organic phases were washed with water, brine, dried (MgSO4), filtered, and concentrated to almost dryness. Ethereal HCl was added (pH 1-2), and the resulting precipitate filtered and dried to afford 25.0 g of the title compound, m.p. 197°-198° C. (dec.). After 3 hours at room temperature the reaction was poured onto ice extracted with diethyl ether The combined organic phases were washed with water, brine dried (MgSO4) filtered concentrated to almost dryness Ethereal HCl was added (pH 1-2) the resulting precipitate filtered dried

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

実験手順: To a 1 L, 3 necked round bottom flask fitted with a mechanical stirrer was added 3-fluoro-2-iodonitrobenzene (3B Medical, 47.7 g, 179 mmol) and 500 mL absolute ethanol. To this stirred solution was added iron powder (325 mesh, Aldrich, 30 g, 537 mmol) followed by dropwise addition of concentrated HCl (30 mL, 360 mmol). The internal temperature rose from 23 to ˜60° C. over the addition. The flask was fitted with a heating mantle and heated with vigorous stirring for 90 minutes. After cooling to room temperature, 1 N sodium carbonate (300 mL) was added followed by ethyl acetate (200 mL). The mixture was stirred for 30 minutes and then filtered through a pad of celite. The celite was washed with ethyl acetate (3×150 mL). The filtrates were placed in a separatory funnel and the water layer was removed. The organic layer was concentrated under reduced pressure to a volume of ˜200 mL, placed in a separatory funnel, diluted with ethyl acetate (400 mL), washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. The crude product was taken up in ether (300 mL) and made acidic to pH 1 with 2M hydrochloric acid/ether (Aldrich). After 1 hour, the tan solid was isolated by filtration (39.2 g, 80%). The above aqueous layers were extracted with diethyl ether (300 mL), dried over sodium sulfate, combined with the filtrate of the 1st crop, made acidic to pH 1, and isolated as above to give additional tan solid (9.0 g, 18%) for an overall yield of 98%. 1H NMR (300 MHz, CDCl3) δ 7.06 (m, 1H), 6.58 (m, 1H), 6.39 (m, 1H), 5.73 (bm, 1H). MS APCI, m/z=238 (M+H). HPLC 2.19 min. To a 1 L, 3 necked round bottom flask fitted with a mechanical stirrer The internal temperature rose from 23 to ˜60° C. over the addition The flask was fitted with a heating mantle heated The mixture was stirred for 30 minutes filtered through a pad of celite The celite was washed with ethyl acetate (3×150 mL) The filtrates were placed in a separatory funnel the water layer was removed The organic layer was concentrated under reduced pressure to a volume of ˜200 mL placed in a separatory funnel diluted with ethyl acetate (400 mL) washed with brine dried over sodium sulfate filtered concentrated to dryness After 1 hour the tan solid was isolated by filtration (39.2 g, 80%) The above aqueous layers were extracted with diethyl ether (300 mL) dried over sodium sulfate isolated as above

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

実験手順: To a 1 L, 3 necked round bottom flask fitted with a mechanical stirrer was added 3-fluoro-2-iodonitrobenzene (3B Medical, 47.7 g, 179 mmol) and 500 mL absolute ethanol. To this stirred solution was added iron powder (325 mesh, Aldrich, 30 g, 537 mmol) followed by dropwise addition of concentrated HCl (30 mL, 360 mmol). The internal temperature rose from 23 to ˜60° C. over the addition. The flask was fitted with a heating mantle and heated with vigorous stirring for 90 minutes. After cooling to room temperature, 1 N sodium carbonate (300 mL) was added followed by ethyl acetate (200 mL). The mixture was stirred for 30 minutes and then filtered through a pad of celite. The celite was washed with ethyl acetate (3×150 mL). The filtrates were placed in a separatory funnel and the water layer was removed. The organic layer was concentrated under reduced pressure to a volume of ˜200 mL, placed in a separatory funnel, diluted with ethyl acetate (400 mL), washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. The crude product was taken up in ether (300 mL) and made acidic to pH 1 with 2M hydrochloric acid/ether (Aldrich). After 1 hour, the tan solid was isolated by filtration (39.2 g, 80%). The above aqueous layers were extracted with diethyl ether (300 mL), dried over sodium sulfate, combined with the filtrate of the 1st crop, made acidic to pH 1, and isolated as above to give additional tan solid (9.0 g, 18%) for an overall yield of 98%. 1H NMR (300 MHz, CDCl3) δ 7.06 (m, 1H), 6.58 (m, 1H), 6.39 (m, 1H), 5.73 (bm, 1H). MS APCI, m/z=238 (M+H). HPLC 2.19 min. To a 1 L, 3 necked round bottom flask fitted with a mechanical stirrer The internal temperature rose from 23 to ˜60° C. over the addition The flask was fitted with a heating mantle heated The mixture was stirred for 30 minutes filtered through a pad of celite The celite was washed with ethyl acetate (3×150 mL) The filtrates were placed in a separatory funnel the water layer was removed The organic layer was concentrated under reduced pressure to a volume of ˜200 mL placed in a separatory funnel diluted with ethyl acetate (400 mL) washed with brine dried over sodium sulfate filtered concentrated to dryness After 1 hour the tan solid was isolated by filtration (39.2 g, 80%) The above aqueous layers were extracted with diethyl ether (300 mL) dried over sodium sulfate isolated as above

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Iodo-3-fluoroaniline hydrochloride (5.7 g, 0.021 mol) was stirred in 7.4 mL of concentrated HCl and cooled to -10° C. An aqueous solution of sodium nitrite (1.63 g, 0.024 mL) in 5 mL water was added dropwise over a 20 minute period, stannous chloride (9.95 g, 0.044 mol) in 12 mL of 6N HCl added at -5° C., warmed to room temperature and stirring continued for 4 hours. The reaction mixture was cooled to 0° C., and made basic with 50% NaOH (pH 10-11), extracted with ether, washed with water, brine, dried (MgSO4), filtered and concentrated to give the hydrazine. Addition of ethereal HCl (pH 1-2) gave 4.6 g of the title compound, m.p. 165°-167° C. warmed to room temperature The reaction mixture was cooled to 0° C. extracted with ether washed with water, brine dried (MgSO4) filtered concentrated

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

実験手順: A solution of 2-iodo-3-fluoronitrobenzene (27.0 g, 0.101 mol) in tetrahydrofuran (200 mL) was added dropwise over a 10 minute period to a stirring solution of stannous chloride dihydrate (68.0 g, 0.302 mol) in concentrated hydrochloric acid (200 mL). After 3 hours at room temperature the reaction was poured onto ice, made alkaline (pH 11) with 50% NaOH, and extracted with diethyl ether. The combined organic phases were washed with water, brine, dried (MgSO4), filtered, and concentrated to almost dryness. Ethereal HCl was added pH 1-2), and the resulting precipitate filtered and dried to afford 25.0 g of the title compound, m.p. 197°-198° C. (dec.). After 3 hours at room temperature the reaction was poured onto ice extracted with diethyl ether The combined organic phases were washed with water, brine dried (MgSO4) filtered concentrated to almost dryness Ethereal HCl was added pH 1-2), and the resulting precipitate filtered dried

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Iodo-3-fluoroaniline hydrochloride (5.7 g, 0.021 mol) was stirred in 7.4 mL of concentrated HCl and cooled to -10° C. An aqueous solution of sodium nitrite (1.63 g, 0.024 mL) in 5 mL water was added dropwise over a 20 minute period, stannous chloride (9.95 g, 0.044 mol) in 12 mL of 6N HCl added at -5° C., warmed to room temperature and stirring continued for 4 hours. The reaction mixture was cooled to 0° C., and made basic with 50% NaOH (pH 10-11), extracted with ether, washed with water, brine, dried (MgSO4), filtered and concentrated to give the hydrazine. Addition of ethereal HCl (pH 1-2) gave 4.6 g of the title compound, m.p. 165°-167° C. warmed to room temperature The reaction mixture was cooled to 0° C. extracted with ether washed with water, brine dried (MgSO4) filtered concentrated

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

実験手順: A solution of 2-iodo-3-fluoronitrobenzene (27.0 g, 0.101 mol) in tetrahydrofuran (200 mL) was added dropwise over a 10 minute period to a stirring solution of stannous chloride dihydrate (68.0 g, 0.302 mol) in concentrated hydrochloric acid (200 mL). After 3 hours at room temperature the reaction was poured onto ice, made alkaline (pH 11) with 50% NaOH, and extracted with diethyl ether. The combined organic phases were washed with water, brine, dried (MgSO4), filtered, and concentrated to almost dryness. Ethereal HCl was added (pH 1-2), and the resulting precipitate filtered and dried to afford 25.0 g of the title compound, m.p. 197°-198° C. (dec.). After 3 hours at room temperature the reaction was poured onto ice extracted with diethyl ether The combined organic phases were washed with water, brine dried (MgSO4) filtered concentrated to almost dryness Ethereal HCl was added (pH 1-2) the resulting precipitate filtered dried