4-Methylmorpholine → benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 249591Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 249591
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12](/[C:14](=[N:18]/[O:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)/[C:15](O)=[O:16])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.Cl.[C:47]1([CH:53]([O:60][C:61]([C:63]2[N:68]3[C:69](=[O:72])[C@@H:70]([NH2:71])[C@H:67]3[S:66][CH2:65][C:64]=2[O:73][S:74]([CH3:77])(=[O:76])=[O:75])=[O:62])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.O>[C:47]1([CH:53]([O:60][C:61]([C:63]2[N:68]3[C:69](=[O:72])[C@@H:70]([NH:71][C:15](=[O:16])/[C:14](/[C:12]4[N:13]=[C:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[S:10][CH:11]=4)=[N:18]\[O:19][C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C@H:67]3[S:66][CH2:65][C:64]=2[O:73][S:74]([CH3:77])(=[O:76])=[O:75])=[O:62])[C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10459636(Z)-2-(2-Boc-aminothiazole-4-yl-)-2-trityloxyiminoacetic acidHCID 883013187beta-Amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride

Produkt 1

HCID 10260338benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of (Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetic acid (41.7 g : 78.8 mMol.) in dichloromethane (600 ml) is added at -30° C. N-methylmorpholine (7.575 g : 75 mMol.), and the mixture is stirred for 10 minutes, mixed with 7β-amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride (37.27 g : 75 mMol.), is stirred at the same temperature for 50 minutes, mixed with 1-ethyl-3-(3dimethylaminopropyl)carbodiimide hydrochloride (14.38 g : 75 mMol.), stirred under ice cooling for 3 hours, diluted with water, and extracted with ethyl acetate. The extract is washed with water, dried, and concentrated under reduced pressure. The residue is purified by silica gel chromatography (toluene containing 0.5% acetic acid : ethyl acetate=10:1) and the eluate is treated with etherhexane to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)- 2-trityloxyiminoacetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (57 .42 g). Colorless powder. Yield: 79%. This product contains ca. 5% of the 2-cephem isomer.

Aufarbeitung

  1. additionis added at -30° C
  2. stirringstirred under ice cooling for 3 hours
  3. extractionextracted with ethyl acetate
  4. washThe extract is washed with water
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by silica gel chromatography (toluene containing 0.5% acetic acid : ethyl acetate=10:1)
  8. additionthe eluate is treated with etherhexane

Quellen und Nachweise

ORD-Eintrag
ord-0f20626356764498b14fb9af31af06a5
Quelldatensatz
uspto-grants-1993_05
Patentnummer
US05214037

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