Propionic Acid → 7-Amino-3-methylenecepham-4-carboxylic acid

HRID 1579983Notes

Reaction equation

HRID 1579983 reaction equation
C=C1C(C([O-])=O)N2C(=O)C[C@H]2SC1.C=C1C(C(O)=O)N2C(=O)C[C@H]2SC1.CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.C(O)(=O)CC.CC(O[CH2:60][C:61]1[CH2:70][S:69][C@@H:64]2[C@H:65]([NH2:68])[C:66](=[O:67])[N:63]2[C:62]=1[C:71]([OH:73])=[O:72])=O.O(CC)C([S-])=S>[Ni]>[CH2:60]=[C:61]1[CH:62]([C:71]([OH:73])=[O:72])[N:63]2[C:66](=[O:67])[CH:65]([NH2:68])[C@H:64]2[S:69][CH2:70]1

Participants

8

Reactant 6

HCID 1032Propionic AcidHCID 4413287-Aminocephalosporanic acidHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterHCID 1248527Carbonodithioic acid, O-ethyl esterHCID 706038793-Methylenecepham-4-carboxylic acid2×HCID 867329163-Methylenecepham-4-carboxylate

Product 1

HCID 130225477-Amino-3-methylenecepham-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

Consequently, when it is desired to prepare a 3-methylenecepham-4-carboxylate of the Formula I, wherein R1 is a carboxylic acid protecting group which is susceptible to cleavage under the conditions of the reductive displacement reaction, the unprotected 3-methylenecepham-4-carboxylic acid can be first prepared. Following the reductive displacement reaction the 3-methylenecepham-4-carboxylic acid reduction product can be isolated and then protected with the desired ester group by esterification or the mixed anhydride thereof with acetic or propionic acid can be prepared according to well known procedures. For example, 3-ethoxythionocarbonylthiomethyl-7-amino-Δ3 -cephem-4-carboxylic acid, obtained by the reaction of 7-aminocephalosporanic acid (7ACA) with ethyl xanthate, is hydrogenated in the presence of Raney nickel to yield 3-methylene-7-aminocepham-4-carboxylic acid. The cepham acid is then acylated and esterified according to known procedures to obtain the desired ester of the Formula I.

Workup

  1. customto cleavage under the conditions of the reductive displacement reaction
  2. customcan be isolated

Sources & evidence

ORD record
ord-e2e9b00390c34a2a9c1185186699cb79
Source dataset
uspto-grants-1976_01
Patent number
US03932393

Reaction notes

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