Trifluoroacetic acid → 7beta-[2-(2-Amino-5-chloro-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 126904Notes

Reaction equation

HRID 126904 reaction equation
C1(C([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:43])[C@@H:24]([NH:25][C:26](=[O:42])[C:27](=[N:39][O:40][CH3:41])[C:28]4[N:29]=[C:30]([NH:34]C(=O)CCl)[S:31][C:32]=4[Cl:33])[C@H:21]3[S:20][CH2:19][CH:18]=2)=[O:16])C2C=CC=CC=2)C=CC=CC=1.NC(N)=S.C(=O)([O-])O.[Na+].C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>C(O)C.O1CCCC1.ClCCl>[CH3:41][O:40][N:39]=[C:27]([C:28]1[N:29]=[C:30]([NH2:34])[S:31][C:32]=1[Cl:33])[C:26]([NH:25][C@@H:24]1[C:23](=[O:43])[N:22]2[C:17]([C:15]([OH:16])=[O:14])=[CH:18][CH2:19][S:20][C@H:21]12)=[O:42]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 516892Sodium BicarbonateHCID 2723790ThioureaHCID 1317121017beta-[2-Methoxyimino-2-(2-chloroacetamido-5-chloro-4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid diphenylmethyl ester

Product 1

HCID 1317121027beta-[2-(2-Amino-5-chloro-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acidYield 78.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7β-[2-methoxyimino-2-(2-chloroacetamido-5-chloro-4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid diphenylmethyl ester (330 mg) in a mixture of ethanol (5 ml) and tetrahydrofuran (5 ml) is added thiourea (152 mg), and the mixture is stirred for 4 hours. After one night, the solution is stirred with 5% aqueous sodium hydrogen carbonate solution for 10 minutes, concentrated to remove organic solvents, and extracted with ethyl acetate. The residue is subjected to silica gel chromatography to give crude 7β-[2-methoxyimino-2-(2-amino-5-chloro-4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid diphenylmethyl ester (273 mg), which is stirred with anisole (0.5 ml) and trifluoroacetic acid (0.5 ml) in dichloromethane (5 ml) under ice-cooling for 1.5 hours, evaporated and treated with ethyl ether and high porous polymer to give 7β-[2-methoxyimino-2-(2-amino-5-chloro-4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid (164 mg). Yield: 76.7%. This product is identical with a sample prepared by another authentic route. Similarly prepared are compounds of Table 1.

Workup

  1. waitAfter one night
  2. concentrationconcentrated
  3. customto remove organic solvents
  4. extractionextracted with ethyl acetate
  5. customto give crude 7β-[2-methoxyimino-2-(2-amino-5-chloro-4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid diphenylmethyl ester (273 mg), which
  6. temperaturecooling for 1.5 hours
  7. customevaporated
  8. additiontreated with ethyl ether and high porous polymer

Sources & evidence

ORD record
ord-256b44d5412444ed8a9cacceeb84c8a5
Source dataset
uspto-grants-1981_03
Patent number
US04254119

Reaction notes

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