Triethylamine → 3-[(Acetyloxy)-methyl]-7-[[2-[4-(chloromethyl)phenyl]-2-carboxyacetyl]-amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1730856

Reaction equation

HRID 1730856 reaction equation
[Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:13]([OH:15])=O)[C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[CH3:16][C:17]([O:19][CH2:20][C:21]1[CH2:30][S:29][C@@H:24]2[C@H:25]([NH2:28])[C:26](=[O:27])[N:23]2[C:22]=1[C:31]([OH:33])=[O:32])=[O:18].[CH2:34]([N:36]([CH2:39][CH3:40])[CH2:37][CH3:38])[CH3:35]>C(Cl)Cl.C(O)CC>[CH2:34]([NH+:36]([CH2:39][CH3:40])[CH2:37][CH3:38])[CH3:35].[C:17]([O:19][CH2:20][C:21]1[CH2:30][S:29][CH:24]2[N:23]([C:26](=[O:27])[CH:25]2[NH2:28])[C:22]=1[C:31]([O-:33])=[O:32])(=[O:18])[CH3:16].[C:17]([O:19][CH2:20][C:21]1[CH2:30][S:29][CH:24]2[N:23]([C:26](=[O:27])[CH:25]2[NH:28][C:13](=[O:15])[CH:9]([C:6]2[CH:5]=[CH:4][C:3]([CH2:2][Cl:1])=[CH:8][CH:7]=2)[C:10]([OH:12])=[O:11])[C:22]=1[C:31]([OH:33])=[O:32])(=[O:18])[CH3:16]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 4413287-Aminocephalosporanic acid2×HCID 22767749p-Chloromethylphenylmalonic acid

Product 2

HCID 203258543-[(Acetyloxy)-methyl]-7-[[2-[4-(chloromethyl)phenyl]-2-carboxyacetyl]-amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 1317101243-[(Acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid triethylammonium salt

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolventHCID 6344DichloromethaneSolvent

Procedure

α-Carboxy-p-chloromethylphenylacetyl nitrophenyl polymer, prepared according to the procedure described in Canadian Patent No. 892,580, carrying 4 m. mole of p-chloromethylphenylmalonic acid is suspended for about 8 hours in 20 ml of dry methylene chloride solution containing 1 m. mole of 3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid triethylammonium salt, which is prepared from 544 mg of 7-aminocephalosporanic acid (1 m. mole) and 0.56 ml of triethylamine (1 m. mole) at room temperature. After only traces of 7-aminocephalosporanic acid remain in solution, which is determined by thin layer chromatography on cellulose in 70% aqueous propanol, the polymer is filtered off and washed with 3 portions of 50 ml each of methylene chloride. The combined filtrates are evaporated and the residue is dissolved in 20 ml or distilled water. This solution is acidified to pH 2 by adding 0.2N hydrochloric acid and extracted twice with ethyl acetate. The organic solution is dried over sodium sulfate and evaporated at room temperature. The remaining solid is dried overnight over phosphorus pentoxide under vacuum to give 3-[(acetyloxy)-methyl]-7-[[2-[4-(chloromethyl)phenyl]-2-carboxyacetyl]-amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

Workup

  1. customα-Carboxy-p-chloromethylphenylacetyl nitrophenyl polymer, prepared
  2. additioncontaining 1 m
  3. filtrationthe polymer is filtered off
  4. washwashed with 3 portions of 50 ml each of methylene chloride
  5. customThe combined filtrates are evaporated
  6. dissolutionthe residue is dissolved in 20 ml
  7. distillationdistilled water
  8. additionby adding 0.2N hydrochloric acid
  9. extractionextracted twice with ethyl acetate
  10. dry with materialThe organic solution is dried over sodium sulfate
  11. customevaporated at room temperature
  12. dry with materialThe remaining solid is dried overnight over phosphorus pentoxide under vacuum

Sources & evidence

ORD record
ord-5accd4cdd1444da980e5c8864763e1e0
Source dataset
uspto-grants-1976_11
Patent number
US03994875

Linked notes

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