(Methylthio)acetic acid → HCID 131711041, compound

HRID 1395773Notes

Reaction equation

HRID 1395773 reaction equation
[NH2:1][CH:2]1[C:21](=[O:22])[N:4]2[C:5]([C:18]([OH:20])=[O:19])=[C:6]([CH2:9][S:10][C:11]3[S:12][C:13]([CH2:16][OH:17])=[N:14][N:15]=3)[CH2:7][S:8][C@H:3]12.[C:23](=O)(O)[O-].[Na+].C[S:29][CH2:30][C:31](O)=O>O.CC(C)=O.S(Cl)(Cl)=O>[CH3:23][CH2:31][C:30]([NH:1][CH:2]1[C:21](=[O:22])[N:4]2[C:5]([C:18]([OH:20])=[O:19])=[C:6]([CH2:9][S:10][C:11]3[S:12][C:13]([CH2:16][OH:17])=[N:14][N:15]=3)[CH2:7][S:8][C@H:3]12)=[S:29]

Participants

7

Reactant 3

HCID 75551(Methylthio)acetic acidHCID 516892Sodium BicarbonateHCID 13121760HCID 13121760, compound

Product 1

HCID 131711041HCID 131711041, compoundYield 88.4%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 24386Thionyl ChlorideSolvent

Procedure

7-Amino-3-(5-hydroxymethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (1.8 g.) was dissolved in a mixture of water (40 ml.), acetone (40 ml.) and sodium bicarbonate (1.26 g.). On the other hand, 2-(methylthio)acetic acid (1.06 g.) was dissolved in a solution (5 ml.) of thionyl chloride. The solution was stirred at room temperature for 30 minutes, and then at 40°-50° C. for 5 minutes. The excess of thionyl chloride was distilled off under reduced pressure. Thus obtained 2-(methylthio) acetyl chloride was dissolved in dried acetone (5 ml.). The acetone solution was added dropwise to the solution obtained above at 0°-5° C. for 15 minutes. The mixture was stirred at the same temperature for an hour, and then at room temperature for an hour. From the reaction mixture, the acetone was distilled off under reduced pressure. The residue was washed with ethyl acetate, and then ethyl acetate (200 ml.) was added to the residue. The solution was adjusted to pH 1.5 with 10% hydrochloric acid, and the ethyl acetate layer was separated out. The remaining aqueous layer was extracted with ethyl acetate (100 ml.) four times. The ethyl acetate extracts were put together, washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate, and then the solvent was evaporated under reduced pressure to give 7-methylthio acetamido-3-(5-hydroxymethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (1.91 g.) m.p. 134°-139° C. (dec.).

Workup

  1. waitat 40°-50° C. for 5 minutes
  2. distillationThe excess of thionyl chloride was distilled off under reduced pressure
  3. dissolutionThus obtained 2-(methylthio) acetyl chloride was dissolved in dried acetone (5 ml.)
  4. additionThe acetone solution was added dropwise to the solution
  5. customobtained above at 0°-5° C. for 15 minutes
  6. stirringThe mixture was stirred at the same temperature for an hour
  7. waitat room temperature for an hour
  8. distillationFrom the reaction mixture, the acetone was distilled off under reduced pressure
  9. washThe residue was washed with ethyl acetate
  10. additionethyl acetate (200 ml.) was added to the residue
  11. customthe ethyl acetate layer was separated out
  12. extractionThe remaining aqueous layer was extracted with ethyl acetate (100 ml.) four times
  13. washwashed with a saturated aqueous solution of sodium chloride
  14. dry with materialdried over magnesium sulfate
  15. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-01328f2dfd5d46c2af5c16695dd12172
Source dataset
uspto-grants-1980_05
Patent number
US04205166

Reaction notes

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