L-Threonine → 2-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 1660373Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1660373
[C:1]1([C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N+]=[N-])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:16]([O:20][C:21]([NH:23][CH:24]1[C:31](=[O:32])[N:30]2[CH:25]1[S:26][CH2:27][C:28]([CH3:36])=[C:29]2[C:33]([OH:35])=[O:34])=[O:22])([CH3:19])([CH3:18])[CH3:17].N[C@H](C(O)=O)[C@@H](C)O>C(#N)C>[CH:7]([O:35][C:33]([C:29]1[N:30]2[CH:25]([S:26][CH2:27][C:28]=1[CH3:36])[CH:24]([NH:23][C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[C:31]2=[O:32])=[O:34])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Komponenten

5

Edukt 3

HCID 6288L-ThreonineHCID 612301,1'-(Diazomethylene)bis(benzene)HCID 128967587-tert.-Butoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene

Produkt 1

HCID 128967622-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneAusbeute 66,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
22 °C

Versuchsvorschrift

A solution of diphenyldiazomethane (116.5 g) in acetonitrile (800 cc) is added dropwise, in the course of 45 minutes, at a temperature of between 25° and 30° C., to a solution of 7-tert.-butyoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (188.6 g) in acetonitrile (2,100 cc). Thr reaction mixture is stirred for 16 hours at 22° C. and is then concentrated to dryness under reduced pressure (20 mm Hg) at 40° C. The residue is redissolved in ethyl acetate (2 liters) and the solution is washed with 2 N hydrochloric acid (700 cc) and then with a saturated aqueous sodium bicarbonate solution (70 cc) and a saturated aqueous sodium chloride solution (700 cc). The solution is dried over sodium sulphate, treated with decolorising charcoal, filtered, and then concentrated to dryness under reduced pressure (20 mm Hg) at 40° C. The residue is dissolved in boiling ethyl acetate (600 cc). Cyclohexane (1 liter) is added, and the mixture is heated to the reflux temperature and then allowed to cool. The crystals which have appeared are filtered off, washed with diethyl ether (3×250 cc) and then dried. 2-Benzhydryloxycarbonyl-7-tert.-butoxycarbonylamino-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (191 g) is obtained in the form of white crystals (m.p.=179° C.). On concentrating the mother liquor to 500 cc, a second fraction of product (32.6 g, m.p.=178° C.) is obtained.

Aufarbeitung

  1. concentrationis then concentrated to dryness under reduced pressure (20 mm Hg) at 40° C
  2. dissolutionThe residue is redissolved in ethyl acetate (2 liters)
  3. washthe solution is washed with 2 N hydrochloric acid (700 cc)
  4. dry with materialThe solution is dried over sodium sulphate
  5. additiontreated with decolorising charcoal
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (20 mm Hg) at 40° C
  8. dissolutionThe residue is dissolved
  9. additionCyclohexane (1 liter) is added
  10. temperaturethe mixture is heated to the reflux temperature
  11. temperatureto cool
  12. filtrationThe crystals which have appeared are filtered off
  13. washwashed with diethyl ether (3×250 cc)
  14. customdried

Quellen und Nachweise

ORD-Eintrag
ord-77e6d9bac1db4c7fb7ef518bc9197b21
Quelldatensatz
uspto-grants-1981_12
Patentnummer
US04307233

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