Formic Acid → Azithromycin

HRID 1356493

反応式

HRID 1356493 の反応式
[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41]([CH3:43])[CH3:42])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[CH2:8][NH:7][C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:51])[CH3:50].C=O.[CH:54](O)=O.O>CC(C)=O>[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41]([CH3:43])[CH3:42])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[CH2:8][N:7]([CH3:54])[C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:51])[CH3:50]

参加物

6

反応物 4

HCID 284Formic AcidHCID 712FormaldehydeHCID 962WaterHCID 98106019-Deoxo-9a-aza-9a-homoerythromycin A

生成物 1

HCID 447043Azithromycin収率 77%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

反応条件

温度
58 °C

実験手順

In a 0.25 L three-necked round bottom flask equipped with a mechanical stirrer, a condenser and thermometer, 25 g of desmethyl-azithromycin was dissolved in 102 mL of acetone. Formaldehyde (5.3 mL) and formic acid (2.6 mL) were added and the clear solution was heated to reflux (˜58° C.). The mixture was maintained under reflux for 3 hours then cooled to less than 40° C. and 102 mL of water was added. The acetone was separated from the reaction mixture by distillation under low vacuum (˜300 mbar). The distillation was stopped when the temperature of the liquid phase reaches ˜40° C./300 mbar. Activated carbon SXI (1.25 g) was added and the suspension was mixed for 1 hour. Then the activated carbon was separated from the solution by filtration on a Büchner filter containing Hyflow. The filter cake was washed with 102 mL of water. The pH was adjusted with an NaOH solution of 47% to 10-10.5 (˜3.14 g). A massive precipitation of Azithromycin was observed. After stirring the suspension for 1 hour, the crude azithromycin was separated by filtration, washed twice with 25 mL of water and dried at 40° C. in a vacuum oven for>24 hours. After drying, 19.7 g of crude azithromycin was obtained (yield 77% based on weight). No impurities that were derivatives of azithromycin were detected.

後処理

  1. customIn a 0.25 L three-necked round bottom flask equipped with a mechanical stirrer, a condenser
  2. temperaturethe clear solution was heated
  3. temperatureThe mixture was maintained
  4. temperatureunder reflux for 3 hours
  5. temperaturethen cooled to less than 40° C.
  6. customThe acetone was separated from the reaction mixture by distillation under low vacuum (˜300 mbar)
  7. distillationThe distillation
  8. customreaches ˜40° C.
  9. additionActivated carbon SXI (1.25 g) was added
  10. additionthe suspension was mixed for 1 hour
  11. customThen the activated carbon was separated from the solution by filtration on a Büchner
  12. filtrationfilter
  13. additioncontaining Hyflow
  14. washThe filter cake was washed with 102 mL of water
  15. customA massive precipitation of Azithromycin
  16. customthe crude azithromycin was separated by filtration
  17. washwashed twice with 25 mL of water
  18. customdried at 40° C. in a vacuum oven for>24 hours
  19. customAfter drying

出典と根拠

ORDレコード
ord-b1980129035f49fcba93284598f2af6a
出典データセット
uspto-grants-2003_07
特許番号
US06586576B2

関連ノート

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