反应详情

温度

70 °C

Under argon, to a suspension of the HCl salt of 4-{[2-(4-morpholinyl)ethyl]oxy}benzoic acid (3.98 g, 13.8 mmol) in CH2Cl2 (100 ml) was added DMF (40 μl), followed with oxalylchloride (3.6 ml, 41.4 mmol). This mixture was then heated to reflux until a clear solution resulted. The reaction mixture was then concentrated, added CH2Cl2 (20 mL) and reconcentrated. A suspension of the above product in CH2Cl2 (100 mL), was added to a suspension of the product of Example 3 (3.96 g, 11.7 mmol) in pyridine (30 mL). This mixture was then heated to 70° C., the CH2Cl2 was distilled off, then stirred for 1 h. CH2Cl2 (200 mL) was added to the cooled reaction mixture, stirred for 15 min and then filtered to provide a first crop of product (crop 1). The filtrate was concentrated in vacuo and the residue taken up in EtOAc, washed with water (4×), brine, dried over Na2SO4, filtered and concentrated to provide Crop 2. Crops 1 and 2 were combined and recrystallized from MeOH to afforded a off white solid (5.54 g, 83%). 1H NMR (400 MHz, DMSO) δ ppm 11.35 (bs, 1H), 10.22 (s, 1H), 8.79 (d, 1H, 0.8 Hz), 7.99 (d, 2H, 8.8 Hz), 7.58-7.64 (m, 3H), 7.37 (t, 1H, 8.0 Hz), 7.12 (d, 2H, 8.8 Hz), 6.95 (s, 2H), 6.84-6.87 (m, 1H), 4.70 (q, 2H, 7.2 Hz), 4.53 (bs, 2H), 3.81-3.98 (m, 4H), 3.49-3.58 (m, 4H), 3.18-3.36 (m, 2H), 1.41 (t, 3H, 7.2 Hz). MS (ES+) m/e 571 [M+H]+.

1. temperatureThis mixture was then heated
2. temperatureto reflux until a clear solution
3. customresulted
4. concentrationThe reaction mixture was then concentrated
5. additionadded CH2Cl2 (20 mL)
6. additionA suspension of the above product in CH2Cl2 (100 mL)
7. distillationthe CH2Cl2 was distilled off
8. additionCH2Cl2 (200 mL) was added to the cooled reaction mixture
9. stirringstirred for 15 min
10. filtrationfiltered
11. customto provide a first crop of product (crop 1)
12. concentrationThe filtrate was concentrated in vacuo
13. washwashed with water (4×), brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated
17. customto provide Crop 2
18. customrecrystallized from MeOH