Reaktion #433562

ord-3fee159cf04141eeb2ad863f9fb88c22

Reaktionsgleichung

Cl
hydrochloric acid
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](COCCO)C3)[C@H](C)[C@H]12
(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[(2S,4S)-2-(2-hydroxyethyloxymethyl)pyrrolidin-4-ylthio]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
O=C([O-])[O-].[K+].[K+]
potassium carbonate
CCOC(C)=N.Cl
ethyl acetimidate hydrochloride
→
CC(=N)N1C[C@@H](SC2=C(C(=O)O)N3C(=O)[C@H]([C@@H](C)O)[C@H]3[C@H]2C)C[C@H]1COCCO
(4R,5S,6S)-3-[(2S,4S)-1-acetimidoyl-2-(2-hydroxyethyloxymethyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Ausbeute 87.4%

Edukte

Cl
hydrochloric acid
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](COCCO)C3)[C@H](C)[C@H]12
(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[(2S,4S)-2-(2-hydroxyethyloxymethyl)pyrrolidin-4-ylthio]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
O=C([O-])[O-].[K+].[K+]
potassium carbonate
CCOC(C)=N.Cl
ethyl acetimidate hydrochloride

Reagenzien

Keine

Lösungsmittel

O=P([O-])([O-])[O-]
phosphate

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Waschenwashed with ethyl acetate
  2. 2
    Einengenconcentrated in vacuo
  3. 3
    SonstigeThe residue was chromatographed on nonionic adsorption resin "Diaion
  4. 4
    Waschen" eluting successively with water and 5% aqueous acetone
  5. 5
    workup.ADDITIONThe fractions containing the desired compound
  6. 6
    Sonstigewere collected

Vorschrift

A solution of (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[(2S,4S)-2-(2-hydroxyethyloxymethyl)pyrrolidin-4-ylthio]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (300 mg) in 0.05M phosphate buffer (pH 7, 30 ml) was adjusted to pH 8.5 with 30% potassium carbonate at 0° C., and ethyl acetimidate hydrochloride (3 g) was added in portions, while adjusting the mixture to around pH 8.5. After stirring for 1 hour, the reaction mixture was neutralized with 1N hydrochloric acid and washed with ethyl acetate and concentrated in vacuo. The residue was chromatographed on nonionic adsorption resin "Diaion HP-20" eluting successively with water and 5% aqueous acetone. The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-3-[(2S,4S)-1-acetimidoyl-2-(2-hydroxyethyloxymethyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (290 mg).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05061804uspto-grants-1991_10