Trifluoroacetic acid → HCID 9826491, compound

HRID 992711Notes

Reaction equation

HRID 992711 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:43]/[OH:44])/[C:8]([NH:10][C@@H:11]2[C:41](=[O:42])[N:13]3[C:14]([C:25]([O:27]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:26])=[C:15]([S:18][CH2:19][C:20]4[CH:21]=[N:22][NH:23][CH:24]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.FC(F)(F)C(O)=O>ClCCl.C1(OC)C=CC=CC=1>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:43]/[OH:44])/[C:8]([NH:10][C@@H:11]2[C:41](=[O:42])[N:13]3[C:14]([C:25]([OH:27])=[O:26])=[C:15]([S:18][CH2:19][C:20]4[CH:21]=[N:22][NH:23][CH:24]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 88157260benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 9826491HCID 9826491, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7519AnisoleSolvent

Procedure

Under nitrogen atmosphere, diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (33.5 g) was suspended in dichloromethane (100 ml) and anisole (35 ml). Trifluoroacetic acid (80 ml) added dropwise below 5° C. for 40 minutes. After stirring below 5° C. for 25 minutes, the reaction mixture was poured into IPE (1.8 l). Resulting precipitate was collected by filtration and dried under reduced pressure. The powder was poured into pH 6.86 buffer (550 ml). The suspension was adjusted to pH 6.9 with 2N-potassium hydroxide, then was stirred at 15° C. until insoluble material disappeared. The solution was subjected to column chromatography on HP-20 (700 ml). The column was washed with water (1.4 l) and the object compound was eluted with 25% aqueous 2-propanol. The active fractions were collected, and adjusted to pH 3.5 with 3N-hydrochloric acid. After stirring at 30° C. for 2 hours, resulting precipitate was filtered and washed with water (50 ml) two times. The precipitate was suspended in water (150 ml), and adjusted to pH 2.0 with 1N-hydrochloric acid. After stirring at room temperature for one hour, the precipitate was collected and washed with water (20 ml). The precipitate was suspended in water (150 ml) again, and then adjusted to pH 2.0 with 1N hydrochloric acid. After stirring at room temperature for one hour, it was adjusted to pH 2.8 with 2N potassium hydroxide. After stirring at the same temperature for 30 minutes, the precipitate was collected, washed with water (20 ml), and dried under reduced pressure to afford 3.75 hydrates of 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylic acid as crystal (9.7 g).

Workup

  1. additionthe reaction mixture was poured into IPE (1.8 l)
  2. customResulting precipitate
  3. filtrationwas collected by filtration
  4. customdried under reduced pressure
  5. additionThe powder was poured into pH 6.86 buffer (550 ml)
  6. stirringwas stirred at 15° C. until insoluble material
  7. washThe column was washed with water (1.4 l)
  8. washthe object compound was eluted with 25% aqueous 2-propanol
  9. customThe active fractions were collected
  10. stirringAfter stirring at 30° C. for 2 hours
  11. customresulting precipitate
  12. filtrationwas filtered
  13. washwashed with water (50 ml) two times
  14. stirringAfter stirring at room temperature for one hour
  15. customthe precipitate was collected
  16. washwashed with water (20 ml)
  17. stirringAfter stirring at room temperature for one hour
  18. stirringAfter stirring at the same temperature for 30 minutes
  19. customthe precipitate was collected
  20. washwashed with water (20 ml)
  21. customdried under reduced pressure

Sources & evidence

ORD record
ord-cd3f9b5709db4274aba27e9271796c7a
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

Loading…