Water → 7-Acetoacetamido-3(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 596789Notes

Reaction equation

HRID 596789 reaction equation
[NH2:1][CH:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][S:10][C:11]3[S:12][C:13]([CH3:16])=[N:14][N:15]=3)[CH2:7][S:8][C@H:3]12.C(=O)([O-])O.[Na+].O.[CH2:28]=[C:29]1[O:33][C:31](=[O:32])[CH2:30]1>CC(C)=O>[C:31]([NH:1][CH:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][S:10][C:11]3[S:12][C:13]([CH3:16])=[N:14][N:15]=3)[CH2:7][S:8][C@H:3]12)(=[O:32])[CH2:30][C:29]([CH3:28])=[O:33]

Participants

6

Reactant 4

HCID 962WaterHCID 12661DiketeneHCID 516892Sodium BicarbonateHCID 129420347-Amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317106607-Acetoacetamido-3(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
5 °C

Procedure

While a mixture of 0.344 g. of 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid, 0.42 g. of sodium hydrogen carbonate, 5 ml. of water and 5 ml. of acetone is stirred under cooling at 5° C, 0.2 g. of diketene is added and the mixture is further stirred at room temperature for 30 minutes. The acetone is removed from the reaction mixture by distillation under reduced pressure and the residual is washed with ethyl acetate. The water layer is separated, adjusted to pH 2 with 50 % phosphoric acid and extracted three times with ethyl acetate. The extracts are pooled, washed with a saturated aqueous solution of sodium chloride, dehydrated over magnesium sulfate, concentrated and allowed to stand under cooling with ice. With the addition of ether the resultant crystals are loosened and recovered by suction-filtration. The procedure gives 7-acetoacetamido-3(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid as crystals melting at 177°-180° C (decomp.). Yield 0.129 g. (30 %).

Workup

  1. additionWhile a mixture of 0.344 g
  2. customThe acetone is removed from the reaction mixture by distillation under reduced pressure
  3. washthe residual is washed with ethyl acetate
  4. customThe water layer is separated
  5. extractionextracted three times with ethyl acetate
  6. washwashed with a saturated aqueous solution of sodium chloride
  7. concentrationconcentrated
  8. temperatureunder cooling with ice
  9. additionWith the addition of ether the resultant crystals
  10. filtrationrecovered by suction-filtration

Sources & evidence

ORD record
ord-f2622ff36d3944a39351e91c9fda1ffd
Source dataset
uspto-grants-1977_03
Patent number
US04012379

Reaction notes

Loading…