Phosphorus oxychloride → 7-[2-(2-(2-thienyl)acetoxyimino)-2-(3-hydroxyphenyl)acetamido]-3-(1methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 126755Notes

Reaction equation

HRID 126755 reaction equation
P(Cl)(Cl)(Cl)=O.[S:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[CH2:11][C:12]([O:14][N:15]=[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=1)[C:17]([OH:19])=O)=[O:13].[NH2:27][CH:28]1[C:46](=[O:47])[N:30]2[C:31]([C:43]([OH:45])=[O:44])=[C:32]([CH2:35][S:36][C:37]3[N:41]([CH3:42])[N:40]=[N:39][N:38]=3)[CH2:33][S:34][C@H:29]12.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(OCC)(=O)C.O.C(Cl)Cl.CN(C)C=O>[S:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[CH2:11][C:12]([O:14][N:15]=[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=1)[C:17]([NH:27][CH:28]1[C:46](=[O:47])[N:30]2[C:31]([C:43]([OH:45])=[O:44])=[C:32]([CH2:35][S:36][C:37]3[N:41]([CH3:42])[N:40]=[N:39][N:38]=3)[CH2:33][S:34][C@H:29]12)=[O:19])=[O:13]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 11708267BistrimethylsilylacetamidHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 539655852-[2-(2-Thienyl)acetoxyimino]-2-(3-hydroxyphenyl)acetic acid

Product 1

HCID 1317114437-[2-(2-(2-thienyl)acetoxyimino)-2-(3-hydroxyphenyl)acetamido]-3-(1methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 71.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
-20 °C

Procedure

Dimethylformamide (0.4 g.), phosphorus oxychloride (0.81 g.), methylene chloride (20 ml.), ethyl acetate (10 ml.) and 2-[2-(2-thienyl)acetoxyimino]-2-(3-hydroxyphenyl)acetic acid (syn isomer) (1.68 g.) were treated in a manner as in example 1(B) to give an ethyl acetate solution. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.64 g.) and bis(trimethylsilyl)acetamide (3.55 g.) were dissolved in ethyl acetate (20 ml.) and stirred at -20° C., to which was added the above obtained solution. Then the reaction mixture was stirred for 1 hour at the same temperature. Water was added thereto and the mixture was stirred for 10 minutes. The ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate. Two ethyl acetate layers were combined. The extract was washed with a saturated aqueous solution of sodium chloride and dried. The solvent was distilled off. The residue was pulverized with a mixed solution of diisopropylether and ether, collected by filtration and washed to give 7-[2-(2-(2-thienyl)acetoxyimino)-2-(3-hydroxyphenyl)acetamido]-3-(1methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (2.2 g.).

Workup

  1. additionwas added the above obtained solution
  2. stirringThen the reaction mixture was stirred for 1 hour at the same temperature
  3. stirringthe mixture was stirred for 10 minutes
  4. customThe ethyl acetate layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washThe extract was washed with a saturated aqueous solution of sodium chloride
  7. customdried
  8. distillationThe solvent was distilled off
  9. filtrationcollected by filtration
  10. washwashed

Sources & evidence

ORD record
ord-6385ced2fb1048b894e94a4a22fb0cff
Source dataset
uspto-grants-1981_03
Patent number
US04254117

Reaction notes

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