ethyl 2-(5-amino-2-fluorophenyl)acetate

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of ethyl 2-(5-amino-2-fluorophenyl)acetate (3.7 g, 18.8 mmol), glycerol (6.92 g, 75.2 mmol), nitrobenzene (4.63 g, 37.6 mmol) and ferrous sulfate (1.06 g, 3.76 mmol) was added conc. sulfuric acid (4.5 mL) dropwise. The reaction mixture was heated at 120° C. for 15 hr. After cooled to RT, the reaction mixture was diluted with ethanol (20 mL), and 2N aq. NaOH was introduced to adjust pH about 13. The resulting mixture was stirred at RT for 1 hr. Then the reaction was neutralized with aq. HCl and filtered, and the dark brown precipitate was washed with methanol. The combined filtrate was concentrated to dryness in vacuum. The resulting residue was washed adequately with methanol and the combined filtrate was concentrated to dryness to give crude product, which was isolated by flash column chromatography to give 2-(6-fluoroquinolin-5-yl)acetic acid and 2-(6-fluoroquinolin-7-yl)acetic acid (1.7 g, 44%). LC-MS (0.05% TFA): [M+1]+ 206.1. 1H-NMR (DMSO-d6, 400 MHz): δ 12.66 (brs, 1H), 8.90 (m, 1H), 8.35 (m, 1H), 8.04 (m, 1H), 7.76 (m, 1H), 7.56 (m, 1H), 3.88 (s, 2H). After cooled to RT was introduced filtered the dark brown precipitate was washed with methanol The combined filtrate was concentrated to dryness in vacuum The resulting residue was washed adequately with methanol the combined filtrate was concentrated to dryness to give crude product which was isolated by flash column chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-amino-2-fluorophenyl)acetic acid (6.13 g, 36.2 mmol) in ethanol (15 mL) was added conc. sulfuric acid (2 mL) dropwise. The reaction mixture was stirred under N2 at 80° C. for 1 hr. After the reaction mixture was cooled to RT and neutralized with aqueous Na2CO3 to pH 7-8, the aqueous solution was extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum to afford ethyl 2-(5-amino-2-fluorophenyl)acetate as a yellow oil which was used for the next step without further purification (6.13 g, 95%). the aqueous solution was extracted with ethyl acetate (3×100 mL) The combined organic layer was washed with brine dried over Na2SO4 evaporated under vacuum

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of ethyl 2-(5-amino-2-fluorophenyl)acetate (3.7 g, 18.8 mmol), glycerol (6.92 g, 75.2 mmol), nitrobenzene (4.63 g, 37.6 mmol) and ferrous sulfate (1.06 g, 3.76 mmol) was added conc. sulfuric acid (4.5 mL) dropwise. The reaction mixture was heated at 120° C. for 15 hr. After cooled to RT, the reaction mixture was diluted with ethanol (20 mL), and 2N aq. NaOH was introduced to adjust pH about 13. The resulting mixture was stirred at RT for 1 hr. Then the reaction was neutralized with aq. HCl and filtered, and the dark brown precipitate was washed with methanol. The combined filtrate was concentrated to dryness in vacuum. The resulting residue was washed adequately with methanol and the combined filtrate was concentrated to dryness to give crude product, which was isolated by flash column chromatography to give 2-(6-fluoroquinolin-5-yl)acetic acid and 2-(6-fluoroquinolin-7-yl)acetic acid (1.7 g, 44%). LC-MS (0.05% TFA): [M+1]+ 206.1. 1H-NMR (DMSO-d6, 400MHz): δ12.66 (brs, 1H), 8.90 (m, 1H), 8.35 (m, 1H), 8.04(m,1H), 7.76 (m, 1H), 7.56 (m, 1H), 3.88(s, 2H). After cooled to RT was introduced filtered the dark brown precipitate was washed with methanol The combined filtrate was concentrated to dryness in vacuum The resulting residue was washed adequately with methanol the combined filtrate was concentrated to dryness to give crude product which was isolated by flash column chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-amino-2-fluorophenyl)acetic acid (6.13 g, 36.2 mmol) in ethanol (15 mL) was added conc. sulfuric acid (2 mL) dropwise. The reaction mixture was stirred under N2 at 80° C. for 1 hr. After the reaction mixture was cooled to RT and neutralized with aqueous Na2CO3 to pH 7-8, the aqueous solution was extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum to afford ethyl 2-(5-amino-2-fluorophenyl)acetate as a yellow oil which was used for the next step without further purification (6.13 g, 95%). the aqueous solution was extracted with ethyl acetate (3×100 mL) The combined organic layer was washed with brine dried over Na2SO4 evaporated under vacuum