3-fluoro-4-hydroxy-5-methoxybenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: To the solution of 3-fluoro-4-hydroxy-5-methoxybenzaldehyde (800 mg, 4.7 mmol) in DCM (50 mL) was added AlCl3 (680 mg, 5.1 mmol) portionwise, and at 0° C., pyridine (950 mg, 9.4 mmol) was added, and the resulting mixture was refluxed overnight. The reaction mixture was quenched with HCl ice-water solution, and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure to give the 3-fluoro-4,5-dihydroxybenzaldehyde as a pale solid (600 mg, yield 81%), which was used directly in the next step without further purification. the resulting mixture was refluxed overnight The reaction mixture was quenched with HCl ice-water solution extracted with EtOAc (50 mL×3) The combined organic layers were washed with brine dried over Na2SO4 concentrated under reduced pressure

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

実験手順: A mixture of 3-fluoro-4-hydroxy-5-methoxybenzaldehyde (50 mg, 0.294 mmol), 1,2-diphenylethanone (57.7 mg, 0.294 mmol), urea (52.9 mg, 0.882 mmol), and concentrated HCl solution (0.5 mL) in ethanol (2 mL) was refluxed at 80° C. for 52 h. The reaction mixture was evaporated under reduced pressure, and the residue was purified by preparative HPLC to give Compound 68 (32.1 mg, yield 28%). 1HNMR (DMSO-d6 400 MHZ): δ 9.25 (s, 1H), 8.70 (s, 1H), 7.49 (s, 1H), 7.32-7.26 (m, 5H), 7.11-7.05 (m, 3H), 6.88 (d, J=1.6 Hz, 2H), 6.86-6.79 (m, 2H), 5.11 (d, J=2.8 Hz, 1H), 3.79 (s, 3H); MS (ESI): m/z 391.0 [M+H]+. The reaction mixture was evaporated under reduced pressure the residue was purified by preparative HPLC

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Anhydrous aluminum chloride (1.11 g, 8.2 mmol) was added to a solution of 3-fluoro-4-hydroxy-5-methoxy benzaldehyde (1.2 g; 6.8 mmol) in dry dichloromethane (16 ml) under an atmosphere of nitrogen. The reaction mixture was cooled down to 0° C., pyridine (2.5 ml; 31 mmol) was slowly added and the solution was heated to reflux and stirred for 24 h. The solution was cooled to 0° C. and 4M aqueous hydrochloric acid was added to the mixture until the pH was approximately 2. The organic phase was discarded and the water phase was extracted with ethyl ether (3×15 ml). The organic extracts were combined then dried over sodium sulfate and concentrated under vacuum to give 3-fluoro-4,5-dihydroxybenzaldehyde (0.904 g; 85% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 9.68 (d, 1H), 7.17 (dd, 1H), 7.16 (br. s, 1H). MS (EI) for C7H5FO3: 157 (MH+). the solution was heated to reflux The solution was cooled to 0° C. the water phase was extracted with ethyl ether (3×15 ml) The organic extracts were combined then dried over sodium sulfate concentrated under vacuum

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

実験手順: Anhydrous aluminum chloride (1.11 g, 8.2 mmol) was added to a solution of 3-fluoro-4-hydroxy-5-methoxy benzaldehyde (1.2 g; 6.8 mmol) in dry dichloromethane (16 ml) under an atmosphere of nitrogen. The reaction mixture was cooled down to 0° C., pyridine (2.5 ml; 31 mmol) was slowly added and the solution was heated to reflux and stirred for 24 h. The solution was cooled to 0° C. and 4M aqueous hydrochloric acid was added to the mixture until the pH was approximately 2. The organic phase was discarded and the water phase was extracted with ethyl ether (3×15 ml). The organic extracts were combined then dried over sodium sulfate and concentrated under vacuum to give 3-fluoro-4,5-dihydroxybenzaldehyde (0.904 g; 85% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 9.68 (d, 1H), 7.17 (dd, 1H), 7.16 (br. s, 1H). MS (EI) for C7H5FO3: 157 (MH+). the solution was heated to reflux The solution was cooled to 0° C. the water phase was extracted with ethyl ether (3×15 ml) The organic extracts were combined then dried over sodium sulfate concentrated under vacuum