1,8-Diazabicyclo(5.4.0)undec-7-ene → 1-(2,2-dimethylpropanoyloxy)ethyl (6R)-3-(methoxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 234126Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 234126
C1CCN2C(=NCCC2)CC1.[NH2:12][CH:13]1[C:26](=[O:27])[N:15]2[C:16]([C:23]([OH:25])=[O:24])=[C:17]([CH2:20][O:21][CH3:22])[CH2:18][S:19][C@H:14]12.[CH3:28][C:29]([CH3:37])([CH3:36])[C:30]([O:32][CH:33](I)[CH3:34])=[O:31].[C:38]([NH:57][C:58]1[S:59][CH:60]=[C:61](/[C:63](=[N:67]/[O:68][C:69]([C:82]2[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=2)([C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)/[C:64](Cl)=[O:65])[N:62]=1)([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(Cl)Cl>[CH3:22][O:21][CH2:20][C:17]1[CH2:18][S:19][C@@H:14]2[CH:13]([NH:12][C:64](=[O:65])/[C:63](/[C:61]3[N:62]=[C:58]([NH:57][C:38]([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[S:59][CH:60]=3)=[N:67]\[O:68][C:69]([C:82]3[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=3)([C:76]3[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=3)[C:70]3[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=3)[C:26](=[O:27])[N:15]2[C:16]=1[C:23]([O:25][CH:33]([O:32][C:30](=[O:31])[C:29]([CH3:37])([CH3:36])[CH3:28])[CH3:34])=[O:24]

Komponenten

6

Edukt 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 128330237-Amino-3-methoxymethyl-3-cephem-4-carboxylic acidHCID 133930641-Iodoethyl 2,2-dimethylpropanoateHCID 14459662(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl chloride

Produkt 1

HCID 144597281-(2,2-dimethylpropanoyloxy)ethyl (6R)-3-(methoxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

9.5 ml (64 mmol) of DBU are slowly added to a suspension of 14.0 g (57 mmol) of 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid in 160 ml of anhydrous methylene chloride at 0° C. and the mixture is subsequently stirred at 0° C. for 30 minutes. 20.8 g (81 mmol) of 1-iodoethyl 2,2-dimethylpropionate are then added and the mixture is stirred at 0° C. for a further 30 minutes and then allowed to warm to room temperature in the course of 30 minutes. After renewed cooling to 0° C., the crude 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetyl chloride (≃54 mmol), dissolved in 100 ml of methylene chloride, is added dropwise and the mixture is then stirred at 0° C. for a further 2 hours. The reaction mixture is concentrated in vacuo and the residue is taken up in ethyl acetate. The mixture is washed successively with 5% sodium thiosulfate solution, saturated sodium bicarbonate solution and saturated sodium chloride solution, and the organic phase is dried over sodium sulfate and concentrated to dryness in vacuo. The crude product is purified by chromatography on silica gel (35-70 μm) (column: 50 cm×8.5 cm, toluene/ethyl acetate=5/1).

Aufarbeitung

  1. stirringthe mixture is stirred at 0° C. for a further 30 minutes
  2. temperatureto warm to room temperature in the course of 30 minutes
  3. temperatureAfter renewed cooling to 0° C.
  4. additionis added dropwise
  5. stirringthe mixture is then stirred at 0° C. for a further 2 hours
  6. concentrationThe reaction mixture is concentrated in vacuo
  7. washThe mixture is washed successively with 5% sodium thiosulfate solution, saturated sodium bicarbonate solution and saturated sodium chloride solution
  8. dry with materialthe organic phase is dried over sodium sulfate
  9. concentrationconcentrated to dryness in vacuo
  10. customThe crude product is purified by chromatography on silica gel (35-70 μm) (column: 50 cm×8.5 cm, toluene/ethyl acetate=5/1)

Quellen und Nachweise

ORD-Eintrag
ord-104cc712127c49859488afd06898e6a5
Quelldatensatz
uspto-grants-1997_01
Patentnummer
US05594133

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