Formic Acid → Azithromycin

HRID 1356492

반응식

HRID 1356492 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

HCID 447043Azithromycin

시약·촉매·용매 1

HCID 180Acetone용매

반응 조건

온도
58 °C

실험 절차

By the methods of the present invention, desmethyl-azithromycin is dissolved in acetone. Formaldehyde and formic acid are added to the solution and the clear solution is heated to reflux (˜58° C.). The mixture is maintained under reflux for about 3 hours then cooled to less than about 40° C. Water is added and the acetone is separated from the reaction mixture by distillation under low vacuum (˜300 mbar). The distillation is stopped when the temperature of the liquid phase reaches ˜40° C./300 mbar. Activated carbon SXI is added and the suspension is mixed for about 1 hour. The activated carbon is then separated from the solution by filtration on a Büchner filter containing Hyflow. The filter cake is washed with water. The pH is adjusted with an NaOH to about 10-10.5 to induce precipitation of azithromycin. The azithromycin suspension is stirred for about 1 hour. The crude azithromycin crude is separated by filtration and washed. Azithromycin is isolated upon drying the filtrate 40° C. in a vacuum oven. Preferably the azithromycin is dried for at least 24 hours. No impurities were detected that were derivatives of azithromycin in the isolated azithromycin Azithromycin dihydrate prepared in accordance with the present invention is suitable formulation and administration for the treatment of susceptible bacterial infections in humans according to the methods and in the amounts set forth in U.S. Pat. No. 4,474,768, cited above.

후처리

  1. temperaturethe clear solution is heated
  2. temperatureThe mixture is maintained
  3. temperatureunder reflux for about 3 hours
  4. temperaturethen cooled to less than about 40° C
  5. customthe acetone is separated from the reaction mixture by distillation under low vacuum (˜300 mbar)
  6. distillationThe distillation
  7. customreaches ˜40° C.
  8. additionActivated carbon SXI is added
  9. additionthe suspension is mixed for about 1 hour
  10. customThe activated carbon is then separated from the solution by filtration on a Büchner
  11. filtrationfilter
  12. additioncontaining Hyflow
  13. washThe filter cake is washed with water
  14. customprecipitation of azithromycin
  15. customThe crude azithromycin crude is separated by filtration
  16. washwashed

출처 및 근거

ORD 기록
ord-dd9974b1ba9e4539a3005f529b19fb00
출처 데이터셋
uspto-grants-2003_07
특허 번호
US06586576B2

연결된 노트

불러오는 중…