2-(4-bromo-2-fluorophenyl)-N-methylacetamide

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

実験手順: A solution of 2-(4-bromo-2-fluorophenyl)-N-methylacetamide (2.479 mmol) in carbon tetrachloride (5 mL) was degassed with a stream of nitrogen for five minutes, at which point the solution was treated with N-bromosuccinimide (2.73 mmol) and azobisisobutyronitrile (0.248 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture stirred at 80° C. overnight. After stirring overnight, the reaction was cooled to room temperature. The reaction mixture was degassed again with a stream of nitrogen for three minutes and was treated with N-bromosuccinimide (0.56 mmol) and azobisisobutyronitrile (0.124 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture stirred at 80° C. for two days. The reaction was then allowed to cool and was concentrated to dryness in vacuo. Purification of the residue by silica gel chromatography (0-50% ethyl acetate/hexanes) afforded the title compound as a white solid (296 mg, 33% yield). 1H NMR (400 MHz, DMSO-d6) d ppm 2.65 (d, J=4.55 Hz, 3 H) 5.81 (s, 1 H) 7.49 (dd, J=8.59, 1.77 Hz, 1 H) 7.61 (dd, J=9.98, 1.89 Hz, 1 H) 7.72 (t, J=8.21 Hz, 1 H) 8.49 (br. s., 1 H). The reaction vessel was purged with nitrogen sealed After stirring overnight the reaction was cooled to room temperature The reaction mixture was degassed again with a stream of nitrogen for three minutes The reaction vessel was purged with nitrogen sealed the mixture stirred at 80° C. for two days to cool was concentrated to dryness in vacuo Purification of the residue by silica gel chromatography (0-50% ethyl acetate/hexanes)

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

実験手順: A solution of 2-(4-bromo-2-fluorophenyl)acetic acid (10.56 mmol) in dichloromethane (20 mL) was treated with oxalyl chloride (31.7 mmol) and dimethylformamide (0.106 mmol). Effervescense was observed for fifteen minutes. When the bubbling had ceased, the reaction was concentrated to dryness in vacuo. The resulting oil was dissolved with dichloromethane and was concentrated to dryness in vacuo. The material was then diluted with tetrahydrofuran (20 mL) and was treated with methanamine (31.7 mmol) dropwise. Effervescense was again observed. A precipitate formed as the reaction was stirred over a two hour period. The contents of the reaction were concentrated to dryness in vacuo and were then dissolved in a minimal amount of methanol. Ethyl acetate was then added to this solution until a solid precipitated. The precipitate was collected by vacuum filtration. In a similar manner, two additional crops were collected from the mother liquor. The resulting solids were combined and triturated with dichloromethane. Purification of the solid by silica gel chromatography (0-5% methanol/dichloromethane) afforded the title compound as a white solid (610 mg, 22% yield). MS(ES)+ m/e 246.0/247.8 [M+H]+ (bromide isotope pattern). Effervescense was observed for fifteen minutes the reaction was concentrated to dryness in vacuo The resulting oil was dissolved with dichloromethane was concentrated to dryness in vacuo The material was then diluted with tetrahydrofuran (20 mL) A precipitate formed as the reaction The contents of the reaction were concentrated to dryness in vacuo were then dissolved in a minimal amount of methanol Ethyl acetate was then added to this solution until a solid precipitated The precipitate was collected by vacuum filtration In a similar manner, two additional crops were collected from the mother liquor triturated with dichloromethane Purification of the solid by silica gel chromatography (0-5% methanol/dichloromethane)