反应详情

温度

0 °C

A 3-necked 2-L round-bottom flask is equipped with an overhead mechanical stirrer and nitrogen flow is maintained. The flask is charged with 7-iodo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde (105 g, 232 mmol), as prepared above, as a suspension in 700 mL of methanol. The mixture is cooled to 0° C., then sodium borohydride (8.76 mmol) is added in three portions over 15 min. The mixture is allowed to warm to ambient temperature and stirred for 2 hours. The solvent is mostly removed in vacuo and the resultant residue is treated with 2.5 L of water and extracted with methylene chloride (4×1.5 L). The combined organic layers are washed with brine (2.5 L), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resultant solid residue is successively treated with 300 mL of methylene chloride and 300 mL of MeOH-EtOAc (1:1). The mixture is swirled at 0° C. for 30 min. The precipitate is filtered by suction, washed with 500 mL of hexane and dried in vacuo at 30° C. yielding [7-iodo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol as an off-white powder: mp 201-203° C. (dec.). 1H NMR (CDCl3, 200 MHz): d 2.26 (s, 3H), 2.62 (m, 8H), 4.02 (s, 2H). 4.39 (s, 4H), 4.93 (m, 2H), 6.05 (br. s, 1H), 7.49 (s, 1H), 7.51 (s, 1H). HRMS (EI+): Calculated for C18H22N3O 3: 455.0706. Found: 455.0699.

1. customA 3-necked 2-L round-bottom flask is equipped with an overhead mechanical stirrer
2. temperaturenitrogen flow is maintained
3. temperatureto warm to ambient temperature
4. customThe solvent is mostly removed in vacuo
5. additionthe resultant residue is treated with 2.5 L of water
6. extractionextracted with methylene chloride (4×1.5 L)
7. washThe combined organic layers are washed with brine (2.5 L)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. additionThe resultant solid residue is successively treated with 300 mL of methylene chloride and 300 mL of MeOH-EtOAc (1:1)
12. waitThe mixture is swirled at 0° C. for 30 min
13. filtrationThe precipitate is filtered by suction
14. washwashed with 500 mL of hexane
15. customdried in vacuo at 30° C.