Phosphorus oxychloride → 7-[2-(2-Aminothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 544024Notes

Reaction equation

HRID 544024 reaction equation
P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH2:18][C:19]#[CH:20])[C:13]([OH:15])=O)[N:11]=1.C[Si](CC(N)=O)(C)C.[NH2:29][CH:30]1[C:40](=[O:41])[N:32]2[C:33]([C:37]([OH:39])=[O:38])=[CH:34][CH2:35][S:36][C@H:31]12.C(=O)(O)[O-].[Na+]>O1CCCC1.O.CN(C)C=O>[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH2:18][C:19]#[CH:20])[C:13]([NH:29][CH:30]2[C:40](=[O:41])[N:32]3[C:33]([C:37]([OH:39])=[O:38])=[CH:34][CH2:35][S:36][C@H:31]23)=[O:15])[N:11]=1

Participants

9

Reactant 5

HCID 24813Phosphorus oxychloride2×HCID 357676Acetamide, 2-(trimethylsilyl)-2×HCID 516892Sodium BicarbonateHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 543726822-(2-Aminothiazol-4-yl)-2-propargyloxyiminoacetic acid

Product 1

HCID 1317124667-[2-(2-Aminothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-cephem-4-carboxylic acidYield 48.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Phosphoryl chloride (1.4 g.) was added dropwise to a suspension of 2-(2-aminothiazol-4-yl)-2-propargyloxyiminoacetic acid (syn isomer, 1.7 g.) in tetrahydrofuran (15 ml.) below 7° C., and stirred at room temperature for 10 minutes. Phosphoryl chloride (1.4 g.), trimethylsilylacetamide (1.3 g.) and N,N-dimethylformamide (0.76 g.) were added to a solution, and stirred for 20 minutes to prepare the activated acid solution. On the other hand, trimethylsilylacetamide (7.8 g.) was added to a suspension of 7-amino-3-cephem-4-carboxylic acid (1.5 g.) in tetrahydrofuran (20 ml.), and stirred at 40° C. for 30 minutes. To the solution was added all at once the activated acid solution obtained above at -20° C., and stirred for 30 minutes at 0° C. After adding water (20 ml.) to the resultant solution at -20° C., the solution was adjusted to pH 7.5 with an aqueous solution of sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and diisopropyl ether in turn, and treated with activated charcoal at pH 5.5. The solution was adjusted to pH 3.0, and the precipitates were collected by filtration and dried over phosphorus pentoxide under reduced pressure to give 7-[2-(2-aminothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 1.47 g.).

Workup

  1. stirringstirred for 20 minutes
  2. customto prepare the activated acid solution
  3. stirringstirred at 40° C. for 30 minutes
  4. additionTo the solution was added all at once the activated acid solution
  5. customobtained above at -20° C.
  6. stirringstirred for 30 minutes at 0° C
  7. customThe aqueous layer was separated
  8. washwashed with ethyl acetate and diisopropyl ether in turn
  9. additiontreated with activated charcoal at pH 5.5
  10. filtrationthe precipitates were collected by filtration
  11. dry with materialdried over phosphorus pentoxide under reduced pressure

Sources & evidence

ORD record
ord-43bcd51e15a94b0b9d3f353ebb2ac39e
Source dataset
uspto-grants-1984_05
Patent number
US04447430

Reaction notes

Loading…