Phosphorus oxychloride → 7-[2-(2-Formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid

HRID 568838Notes

Reaction equation

HRID 568838 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][C:11]([Br:21])=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:22][CH:23]1[C:41](=[O:42])[N:25]2[C:26]([C:38]([OH:40])=[O:39])=[C:27]([CH2:30][S:31][C:32]3[S:33][C:34]([CH3:37])=[N:35][N:36]=3)[CH2:28][S:29][C@H:24]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][C:11]([Br:21])=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([NH:22][CH:23]2[C:41](=[O:42])[N:25]3[C:26]([C:38]([OH:40])=[O:39])=[C:27]([CH2:30][S:31][C:32]4[S:33][C:34]([CH3:37])=[N:35][N:36]=4)[CH2:28][S:29][C@H:24]23)=[O:17])[N:13]=1)=[O:7]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 129420347-Amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 538011022-(2-Formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetic acid

Product 1

HCID 1317153357-[2-(2-Formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acidYield 59.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent4×

Procedure

A mixture of dimethylformamide (0.3 ml.), phosphoryl chloride (0.35 ml.) and dry ethyl acetate (1.5 ml.) was stirred for 30 minutes under ice-cooling. Dry ethyl acetate (1.5 ml.) and 2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer, 1.0 g.) were added to the solution and stirred for 50 minutes under ice-cooling. The solution was added dropwise to a chilled solution of 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid (1.1 g.) and trimethylsilylacetamide (2.5 g.) in dry ethyl acetate (30 ml.), and stirred at -20° to -10° C. for an hour. To the reaction mixture were added ethyl acetate (30 ml.) and water 20 ml., and the insoluble substance was filtered off. The ethyl acetate layer was separated from the filtrate, and the aqueous layer was washed with ethyl acetate. The washings and the ethyl acetate layer were combined together, washed with a saturated aqueous sodium chloride, dried over magnesium sulfate and then evaporated in vacuo. The residue was pulverized with diethyl ether, and the precipitates were collected by filtration, washed with diethyl ether and dried to give 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid (syn isomer, 1.2 g.).

Workup

  1. temperaturecooling
  2. stirringstirred for 50 minutes under ice-
  3. temperaturecooling
  4. stirringstirred at -20° to -10° C. for an hour
  5. filtration, and the insoluble substance was filtered off
  6. customThe ethyl acetate layer was separated from the filtrate
  7. washthe aqueous layer was washed with ethyl acetate
  8. washwashed with a saturated aqueous sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. customevaporated in vacuo
  11. filtrationthe precipitates were collected by filtration
  12. washwashed with diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-38ada20462c44f408720b6cddf061fec
Source dataset
uspto-grants-1988_03
Patent number
US04729991

Reaction notes

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