反应详情

9-aminominocycline sulfate salt (1.0 g, 1.50 mmol) is dissolved in DMF (50 mL) and treated with a solution of 2-chloro-1,1,1-trimethoxyethane (0.463 g, 3.00 mmol, 2 equivalents). The reaction is stirred at room temperature until mass spectrometry shows conversion to the chloromethylbenzoxazole derivative. The solution is then treated with n-propylamine (10 mL, excess) and stirred until mass spectrometry shows conversion to the n-propylaminomethyl benzoxazole. The mixture is concentrated under reduced pressure to remove excess n-propylamine, and then poured slowly into ether (1 L) and HCl/ether is added to precipate the salt. The solid is rinsed with fresh ether and dried under vacuum. The crude solid is dissolved in water (100 mL) giving a solution at pH 2. The pH is raised successively by 0.5 units with aqueous ammonia, and extracted with dichloromethane. The fractions extracted at pH 4-4.5 are combined, dried (Na2SO4), filtered and concentrated nearly to dryness. A small volume of methanol is added and the solution is treated with 1M HCl in ether. The precipitated solid is collected by filtration, washed with fresh ether and dried under vacuum to yield 0.067 g of the product as its HCl salt.

1. stirringstirred until mass spectrometry
2. concentrationThe mixture is concentrated under reduced pressure
3. customto remove excess n-propylamine
4. additionpoured slowly into ether (1 L) and HCl/ether
5. additionis added
6. washThe solid is rinsed with fresh ether
7. customdried under vacuum
8. dissolutionThe crude solid is dissolved in water (100 mL)
9. customgiving a solution at pH 2
10. extractionextracted with dichloromethane
11. extractionThe fractions extracted at pH 4-4.5
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated nearly to dryness
15. additionA small volume of methanol is added
16. additionthe solution is treated with 1M HCl in ether
17. filtrationThe precipitated solid is collected by filtration
18. washwashed with fresh ether
19. customdried under vacuum