Acetamide, N-(trimethylsilyl)- → Sodium 7-[2-(2-aminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylate

HRID 34499Notes

Reaction equation

HRID 34499 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:11][O:12][CH:13]([F:15])[F:14])[C:8]([OH:10])=O)[N:6]=1.C(N(C(C)C)CC)(C)C.S(Cl)(C)(=O)=O.[NH2:30][CH:31]1[C:43](=[O:44])[N:33]2[C:34]([C:40]([OH:42])=[O:41])=[C:35]([CH2:38][OH:39])[CH2:36][S:37][C@H:32]12.C[Si](C)(C)NC(=O)C.C(=O)(O)[O-].[Na+:57]>CN(C)C=O.O.O1CCCC1>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:11][O:12][CH:13]([F:15])[F:14])[C:8]([NH:30][CH:31]2[C:43](=[O:44])[N:33]3[C:34]([C:40]([O-:42])=[O:41])=[C:35]([CH2:38][OH:39])[CH2:36][S:37][C@H:32]23)=[O:10])[N:6]=1.[Na+:57]

Participants

10

Reactant 6

HCID 25989Acetamide, N-(trimethylsilyl)-HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 129054807-Amino-3-hydroxymethyl-3-cephem-4-carboxylic AcidHCID 538203242-(2-Aminothiazol-4-yl)-2-difluoromethoxyiminoacetic acid

Product 1

HCID 131715672Sodium 7-[2-(2-aminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylateYield 38.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

To a solution of 2-(2-aminothiazol-4-yl)-2-difluoromethoxyiminoacetic acid (syn isomer) (948 mg) in N,N-dimethylformamide (20 ml) were added diisopropylethylamine (1.04 g) and mesyl chloride (920 mg) at -50° C., and the mixture was stirred for 30 minutes at the same temperature. On the other hand, a mixture of 7-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid (1.0 g), N-trimethylsilylacetamide (16 g) and tetrahydrofuran (32 ml) was stirred for one hour at room temperature, cooled to -45° C. and added all at once to the above obtained activated acid solution, and the mixture was stirred for 2 hours at -40° to -30° C. The reaction mixture was poured into a solution of sodium bicarbonate (1.68 g) in water (100 ml) and the mixture was washed with ethyl acetate (50 ml). The aqueous solution was adjusted to pH 3-4 with 10% hydrogen chloride, salted out and extracted twice with a mixture of tetrahydrofuran (50 ml) and ethyl acetate (50 ml). The extract was washed three times with an aqueous solution of sodium chloride and dried over magnesium sulfate. To the extract was added a solution of sodium 2-ethylhexanoate (0.66 g) in ether (25 ml) and the resulting precipitates were collected by filtration to give sodium 7-[2-(2-aminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylate (syn isomer) (0.73 g).

Workup

  1. stirringwas stirred for one hour at room temperature
  2. additionadded all at once to the
  3. customabove obtained
  4. stirringthe mixture was stirred for 2 hours at -40° to -30° C
  5. washthe mixture was washed with ethyl acetate (50 ml)
  6. extractionextracted twice with a mixture of tetrahydrofuran (50 ml) and ethyl acetate (50 ml)
  7. washThe extract was washed three times with an aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. additionTo the extract was added a solution of sodium 2-ethylhexanoate (0.66 g) in ether (25 ml)
  10. customthe resulting precipitates
  11. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-6c43dbf1b72842afbbbbed515f814387
Source dataset
uspto-grants-1988_08
Patent number
US04761410

Reaction notes

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