Triethylamine → Cefotaxime

HRID 362590

Reaktionsgleichung

Reaktionsgleichung von HRID 362590
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:11]/[O:12][CH3:13])/[C:8]([OH:10])=O)[N:6]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:33][C:34]([O:36][CH2:37][C:38]1[CH2:47][S:46][C@@H:41]2[C@H:42]([NH2:45])[C:43](=[O:44])[N:40]2[C:39]=1[C:48]([OH:50])=[O:49])=[O:35].C(N(CC)CC)C>O1CCCC1.CN(C)C(=O)C.O.C(O)(=O)C>[CH3:33][C:34]([O:36][CH2:37][C:38]1[CH2:47][S:46][C@@H:41]2[C@H:42]([NH:45][C:8](/[C:7](/[C:5]3[N:6]=[C:2]([NH2:1])[S:3][CH:4]=3)=[N:11]\[O:12][CH3:13])=[O:10])[C:43](=[O:44])[N:40]2[C:39]=1[C:48]([OH:50])=[O:49])=[O:35]

Komponenten

9

Edukt 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 4413287-Aminocephalosporanic acidHCID 5486924(alphaZ)-2-Amino-alpha-(methoxyimino)-4-thiazoleacetic acid

Produkt 1

HCID 5742673Cefotaxime

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

2,2'-Dithio-bis-5-methyl-1,3,4-thiadiazole (48.09 g) and (Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid (23.38 g) were suspended in tetrahydrofuran (297 ml) and triphenylphosphine (48.09) was added at 20°-25° C. This mixture was stirred for half an hour to generate 2-mercapto-5-methyl-1,3,4-thiadiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetate in solution. Thereafter, the reaction mixture was cooled to 3°-5° C., diluted with N,N-dimethylacetamide (46.8 ml), water (297 ml) and 7-aminocephalosporanic acid (27.2 g) was added, followed by triethylamine addition in 20 min. The reaction was continued for 3-4 hours at 3°-5° C. Thereafter, acetic acid (18 g) and water (100 ml) were added and the aqueous layer was thoroughly extracted with methylene chloride to remove tetrahydrofuran and other by-products. The aqueous phase containing triethylamine salt of cefotaxime acid was mixed with excess isopropyl alcohol (250 ml) and acidified to pH 2.80 at 0°-5°° C. with hydrochloric acid to precipitate cefotaxime acid. The mixture was then filtered, the solids washed with water, isopropyl alcohol and dried to obtain cefotaxime acid.

Aufarbeitung

  1. temperatureThereafter, the reaction mixture was cooled to 3°-5° C.
  2. additionwas added
  3. extractionthe aqueous layer was thoroughly extracted with methylene chloride
  4. customto remove tetrahydrofuran and other by-products
  5. additionThe aqueous phase containing triethylamine salt of cefotaxime acid
  6. additionwas mixed with excess isopropyl alcohol (250 ml)
  7. customacidified to pH 2.80 at 0°-5°° C
  8. customwith hydrochloric acid to precipitate cefotaxime acid
  9. filtrationThe mixture was then filtered
  10. washthe solids washed with water, isopropyl alcohol
  11. customdried

Quellen und Nachweise

ORD-Eintrag
ord-6b1ea39a5b6c4a2999cf84051403682a
Quelldatensatz
uspto-grants-1999_02
Patentnummer
US05869649

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