Sodium Bicarbonate → 7-[2-methoxyimino-2-(2,3-dihydro-1,4-dithiin-5-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 648401Notes

Reaction equation

HRID 648401 reaction equation
[CH3:1][O:2][N:3]=[C:4]([C:8]1[S:9][CH2:10][CH2:11][S:12][CH:13]=1)[C:5]([OH:7])=O.[NH2:14][CH:15]1[C:36](=[O:37])[N:17]2[C:18]([C:33]([OH:35])=[O:34])=[C:19]([CH2:22][S:23][C:24]3[N:28]([CH2:29][C:30]([OH:32])=[O:31])[N:27]=[N:26][N:25]=3)[CH2:20][S:21][C@H:16]12.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CC(C)=O>[CH3:1][O:2][N:3]=[C:4]([C:8]1[S:9][CH2:10][CH2:11][S:12][CH:13]=1)[C:5]([NH:14][CH:15]1[C:36](=[O:37])[N:17]2[C:18]([C:33]([OH:35])=[O:34])=[C:19]([CH2:22][S:23][C:24]3[N:28]([CH2:29][C:30]([OH:32])=[O:31])[N:27]=[N:26][N:25]=3)[CH2:20][S:21][C@H:16]12)=[O:7]

Participants

7

Reactant 3

HCID 516892Sodium Bicarbonate2×HCID 127691497-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 539358522-Methoxyimino-2-(2,3-dihydro-1,4-dithiin-5-yl)acetic acid

Product 1

HCID 1317124017-[2-methoxyimino-2-(2,3-dihydro-1,4-dithiin-5-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 78%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Ethyl acetate (15 ml.) and 2-methoxyimino-2-(2,3-dihydro-1,4-dithiin-5-yl)acetic acid (syn isomer) (2.0 g.) were added to the solution at -10° C. to give a solution. On the other hand, a suspension of 7-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (2.83 g.) in water (40 ml.) was changed to a solution by adding sodium bicarbonate (1.45 g.), and then acetone (40 ml.) was added thereto. After the solution was adjusted to pH7.3, the ethyl acetate solution obtained above was added dropwise thereto over 10 minutes with stirring at -5° to -7° C., during which the pH of the mixture was kept at 6.8 to 7.3 with an aqueous solution of sodium bicarbonate. The mixture was stirred for 1.5 hours at the same temperature. The resultant solution was adjusted to pH7.8 and washed with ethyl acetate (40 ml.). The solution was adjusted to pH6 and washed with ethyl acetate (40 ml.). And the solution was adjusted to pH2 and extracted with ethyl acetate (100 ml.). The extract was washed with a saturated aqueous solution of sodium chloride (60 ml.) and dried over magnesium sulfate. The extract was concentrated in vacuo, and the residue was washed with diethyl ether and collected by filtration to give pale yellow crystals of 7-[2-methoxyimino-2-(2,3-dihydro-1,4-dithiin-5-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (3.4 g.).

Workup

  1. customto give a solution
  2. additionabove was added dropwise
  3. stirringThe mixture was stirred for 1.5 hours at the same temperature
  4. washwashed with ethyl acetate (40 ml.)
  5. washwashed with ethyl acetate (40 ml.)
  6. extractionextracted with ethyl acetate (100 ml.)
  7. washThe extract was washed with a saturated aqueous solution of sodium chloride (60 ml.)
  8. dry with materialdried over magnesium sulfate
  9. concentrationThe extract was concentrated in vacuo
  10. washthe residue was washed with diethyl ether
  11. filtrationcollected by filtration

Sources & evidence

ORD record
ord-abed65756a6d489480ea5a5309908107
Source dataset
uspto-grants-1983_10
Patent number
US04411898

Reaction notes

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