Pyridine → tert-butyl (6R,7R)-8-oxo-3-[(2R)-oxolan-2-yl]-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 376565Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 376565
CS(Cl)(=O)=O.[C:6]([NH:25][C:26]1[S:27][CH:28]=[C:29](/[C:31](=[N:35]/[O:36][C:37]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)/[C:32]([O-])=[O:33])[N:30]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Na+].[NH2:57][C@@H:58]1[C:77](=[O:78])[N:60]2[C:61]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])=[C:62]([C@H:65]3[CH2:69][CH2:68][CH2:67][O:66]3)[CH2:63][S:64][C@H:59]12.N1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[O:66]1[CH2:67][CH2:68][CH2:69][C@@H:65]1[C:62]1[CH2:63][S:64][C@@H:59]2[C@H:58]([NH:57][C:32](=[O:33])/[C:31](/[C:29]3[N:30]=[C:26]([NH:25][C:6]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=4)[S:27][CH:28]=3)=[N:35]\[O:36][C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:77](=[O:78])[N:60]2[C:61]=1[C:70]([O:72][C:73]([CH3:75])([CH3:74])[CH3:76])=[O:71]

Komponenten

7

Edukt 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 10381740t-butyl (6R,7R)-7-amino-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylateHCID 23714200sodium (2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetate

Produkt 1

HCID 172930684tert-butyl (6R,7R)-8-oxo-3-[(2R)-oxolan-2-yl]-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Methanesulphonyl chloride (96μl, 1.25mmol) was added to sodium 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetate (852mg, 1.2mmol) in DMF (2ml) at <-40° C. The mixture was stirred 0.5h at -30±10° C. then t-butyl (6R,7R)-7-amino-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (326mg, 1mmol) in DMF (2ml), followed by pyridine (101μl, 1.25mmol), were added. The reaction was stirred for 1h without further cooling then diluted with ethyl acetate, washed twice with water and with brine, dried, concentrated in vacuo and flash chromatographed eluting with 25, 30% ethyl acetate in hexane to give the title compound as a colourless foam (665mg, 68%); vmax (CH2Cl2) 3395, 1787, 1722, 1687, 1527, 1449, 1156 and 1051cm-1 ; δH (CDCl3 /CD3OH) 1.55 (9H, s), 1.65-2.25 (4H, m), 3.32 and 3.40 (2H, ABq, J 17.6Hz), 3.8-4.0 (2H, m), 5.08 (1H, d, J 4.8Hz), 5.13 (1H, dd, J 7.0, 8.1Hz), 5.91 (1H, d, J 4.5Hz), 6.56 (1H, s), 7.2-7.5 (30H, m). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (1002)].

Aufarbeitung

  1. additionwere added
  2. temperaturewithout further cooling
  3. washwashed twice with water and with brine
  4. customdried
  5. concentrationconcentrated in vacuo and flash
  6. customchromatographed
  7. washeluting with 25, 30% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-9bae6efc9c4e42f0a95829a95fdf6f4c
Quelldatensatz
uspto-grants-2000_02
Patentnummer
US06020329

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