Methanol → t-butyl (6R,7R)-7-amino-3-[(5S)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylate

HRID 6290

Reaktionsgleichung

Reaktionsgleichung von HRID 6290
P(Cl)(Cl)(Cl)(Cl)Cl.[O:7]=[C:8]1[CH2:12][CH2:11][C@@H:10]([C:13]2[CH2:14][S:15][C@@H:16]3[C@H:27]([NH:28]C(=O)COC4C=CC=CC=4)[C:26](=[O:39])[N:17]3[C:18]=2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[O:9]1.CN1CCOCC1.CO>ClCCl.O>[NH2:28][C@@H:27]1[C:26](=[O:39])[N:17]2[C:18]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[C:13]([C@H:10]3[O:9][C:8](=[O:7])[CH2:12][CH2:11]3)[CH2:14][S:15][C@H:16]12

Komponenten

7

Edukt 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 57285999t-butyl (6R,7R)-3-[(5S)-2-oxotetrahydrofuran-5-yl]-7-phenoxyacetamido-ceph-3-em-4-carboxylate

Produkt 1

HCID 57283631t-butyl (6R,7R)-7-amino-3-[(5S)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylateAusbeute 40,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

Phosphorus pentachloride (0.35 g,1.7 mmol) in dichloromethane (9 ml) was added to t-butyl (6R,7R)-3-[(5S)-2-oxotetrahydrofuran-5-yl]-7-phenoxyacetamido-ceph-3-em-4-carboxylate (0.526 g, 1.1 mmol) and N-methylmorpholine (0.24 ml, 2.2 mmol) in dichloromethane (15 ml) at <-20° C. The reaction was stirred at -15±5° C. for 0.75 h then methanol (3 ml) was added. Stirring was continued for 0.75 h without further cooling and then water (10 ml) was added and the mixture was stirred vigorously for 1 h. The dichloromethane was removed in vacuo, ethyl acetate (ca 10 ml) added, the mixture adjusted to pH5.5 with dilute ammonium hydroxide solution and extracted twice with ethyl acetate. The extracts were washed with brine, dried, concentrated and flash chromatographed, eluting with 40,50,75% ethyl acetate in hexane, to give the title compound as a foam (0.15 g,40%); (Found: M+, 340.1097. C15H20N2O5S requires M, 340.1093); νmax (CH2Cl2) 1770,1710,1362,1350,1235 and 1170 cm-1 ; δH (CDCl3) 1.54 (9H,s), 1.9-2.1 (1H,m), 2.5-2.8 (3H,m), 3.27 and 3.56 (2H,ABq,J18.5 Hz), 4.80 (1H,d,J5Hz), 4.96 (1H,d,J5 Hz), 5.6-5.7 (1H,m).

Aufarbeitung

  1. stirringStirring
  2. waitwas continued for 0.75 h
  3. temperaturewithout further cooling
  4. stirringthe mixture was stirred vigorously for 1 h
  5. customThe dichloromethane was removed in vacuo, ethyl acetate (ca 10 ml)
  6. additionadded
  7. extractionextracted twice with ethyl acetate
  8. washThe extracts were washed with brine
  9. customdried
  10. concentrationconcentrated
  11. customflash chromatographed
  12. washeluting with 40,50,75% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-9ec0a0a647af429cbc50491e9b181fb6
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05246926

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