Reaction #155416

ord-62f5b10b7d794c21bde5c1df8ca5fed7

Reaction equation

CCN(CC)CC
Triethylamine
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
Intermediate 1
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
(1S,4S)-4-nitrobenzyl 3-oxo-2-thia-5-azabicylco[2.2.1]heptane-5-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
raw material 3
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
CCOC(C)=O
ethyl acetate
→
CC(=O)O.NCc1ccc(S(N)(=O)=O)cc1
solid
CC(=O)O.NCc1ccc(S(N)(=O)=O)cc1
mafenide acetate

Reactants

CCN(CC)CC
Triethylamine
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
Intermediate 1
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
(1S,4S)-4-nitrobenzyl 3-oxo-2-thia-5-azabicylco[2.2.1]heptane-5-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
raw material 3
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
CCOC(C)=O
ethyl acetate

Reagents

None

Solvents

CN(C)C=O
dimethylformamide

Conditions

Temperature
-15°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.ADDITIONwas added
  2. 2
    WashThe mixture was sequentially washed with water, dilute hydrochloric acid and saturated sodium bicarbonate
  3. 3
    Dryingthe organic layer was dried over anhydrous sodium sulfate
  4. 4
    ConcentrationThe ethyl acetate layer was concentrated
  5. 5
    Filtrationthe precipitate was filtered
  6. 6
    Otherdried

Procedure

Intermediate 1 and (4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (raw material 3) (2980 g, 5.01 mol) were dissolved in dimethylformamide, and the solution was cooled to −15° C. Triethylamine was added dropwise under nitrogen protection. After the reaction is over, ethyl acetate was added. The mixture was sequentially washed with water, dilute hydrochloric acid and saturated sodium bicarbonate, and the organic layer was dried over anhydrous sodium sulfate. The ethyl acetate layer was concentrated and the precipitate was filtered, and dried to obtain 3300 g of a solid (i.e. intermediate 2) with a yield of 79.46% and a purity of 94.75%.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08822445B2uspto-grants-2014_09