反应详情

温度

110 °C

In a round-bottom flask was charged 3-(2-(R)-methyl-pyrrolidin-1-yl)-propionic acid ethyl ester (5.6 g, 30 mmol), 4-bromo-benzene-1,2-diamine (5.6 g, 30 mmol) and 56 mL of 5% P2O5 in CH3SO3H (Eaton's reagent). After briefly stirring, the homogeneous solution was heated to 110° C. for approximately 24–48 h. The reaction mixture was quenched with ice (˜50 g) and then the pH slowly adjusted to pH >11 with 50% NaOH. The product was extracted with isopropyl acetate (100 mL). The organic layer was then extracted with 5% NaHCO3, H2O and then distilled to dryness. The crude product was purified by column chromatography to provide the title compound (3.7 g). 1H NMR (500 MHz, [(CD3)2SO] δ 1.00 (d, 3H), 1.27 (m, 1H), 1.63 (m, 2H), 1.85 (m, 1H), 2.11 (m, 1H), 2.31 (m, 1H), 2.45 (m, 1H), 2.91–2.99 (m, 2H), 3.09 (m, 1H), 3.19 (m, 1H), 7.24 (m, 1H), 7.43 (d, 1H), 7.66 (s, 1H), some protons were not readily identified due to exchange broadening. 13C NMR (500 MHz, [(CD3)2SO+2 drops DCI] δ 15.3, 21.0, 23.2, 31.0, 48.3, 52.3, 64.3, 115.9, 116.6, 117.9, 128.8, 130.2, 132.2, 151.1 (some 13C peaks were not readily identified due to exchange broadening at 25° C., but were observed under acidic conditions, 2 drops DCI). APPI-MS: (M+1)+ at 308 m/z.

1. customThe reaction mixture was quenched with ice (˜50 g)
2. extractionThe product was extracted with isopropyl acetate (100 mL)
3. extractionThe organic layer was then extracted with 5% NaHCO3, H2O
4. distillationdistilled to dryness
5. customThe crude product was purified by column chromatography