Tetrahydrofuran → Desacetylcefotaxime

HRID 1649752Notes

Reaction equation

HRID 1649752 reaction equation
C1COCC1.[NH2:6][C@@H:7]1[C:19](=[O:20])[N:9]2[C:10]([C:16]([OH:18])=[O:17])=[C:11]([CH2:14][OH:15])[CH2:12][S:13][C@H:8]12.C(=O)([O-])O.[Na+].Cl.ClCC([NH:31][C:32]1[S:33][CH:34]=[C:35](/[C:37](=[N:41]/[O:42][CH3:43])/[C:38](Cl)=[O:39])[N:36]=1)=O>O.O1CCCC1.C(OCC)(=O)C.O>[NH2:31][C:32]1[S:33][CH:34]=[C:35](/[C:37](=[N:41]/[O:42][CH3:43])/[C:38]([NH:6][C@@H:7]2[C:19](=[O:20])[N:9]3[C:10]([C:16]([OH:18])=[O:17])=[C:11]([CH2:14][OH:15])[CH2:12][S:13][C@H:8]23)=[O:39])[N:36]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 11031679(6R-trans)-7-Amino-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 12884125(2Z)-2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-methoxyiminoacetyl chloride;hydrochloride

Product 1

HCID 9576239DesacetylcefotaximeYield 63.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

In 800 ml of water-tetrahydrofuran (briefly, THF) (1:1) is suspended 16.9 g of 7β-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, and with ice-cooling and stirring, 27.72 g of sodium hydrogen carbonate is added. Then, 29.4 g of 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetyl chloride hydrochloride is added gradually thereto and the mixture is stirred for 30 minutes. To this reaction mixture are added 150 ml of water and 200 ml of ethyl acetate and the water layer is separated. Under ice-cooling and stirring, this water layer is adjusted to pH 7.0 with 1N-hydrochloric acid. Under stirring at room temperature, 18.9 g of sodium N-methyldithiocarbamate is added gradually to thereby eliminate the aminoprotective group (This is confirmed by TLC). To the reaction mixture is added 300 ml of ethyl acetate and the water layer is separated and concentrated under reduced pressure to 70 ml. The residue is chromatographed on a column of XAD-II (1 l) and eluted with water. The fractions rich in the desired compound are pooled and concentrated to 100 ml, and with ice-cooling and stirring, the residue is adjusted to pH 2.5 with 4N-hydrochloric acid. The resulting crystals are collected by filtration, washed with 100 ml of water, 50 ml of ethyl acetate and 50 ml of THF, and dried under reduced pressure. The above procedure yields 19.3 g of 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid

Workup

  1. temperaturewith ice-cooling
  2. stirringthe mixture is stirred for 30 minutes
  3. customthe water layer is separated
  4. temperatureUnder ice-cooling
  5. stirringstirring
  6. stirringUnder stirring at room temperature
  7. addition18.9 g of sodium N-methyldithiocarbamate is added gradually
  8. additionTo the reaction mixture is added 300 ml of ethyl acetate
  9. customthe water layer is separated
  10. concentrationconcentrated under reduced pressure to 70 ml
  11. customThe residue is chromatographed on a column of XAD-II (1 l)
  12. washeluted with water
  13. concentrationconcentrated to 100 ml
  14. temperaturewith ice-cooling
  15. stirringstirring
  16. filtrationThe resulting crystals are collected by filtration
  17. washwashed with 100 ml of water, 50 ml of ethyl acetate and 50 ml of THF
  18. customdried under reduced pressure

Sources & evidence

ORD record
ord-0b6883a3b2d84b218a4ef39f2fb166d1
Source dataset
uspto-grants-1990_05
Patent number
US04921851

Reaction notes

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