Phosphorus oxychloride → HCID 131712325, compound

HRID 745409Notes

Reaction equation

HRID 745409 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:30][CH:31]1[C:41](=[O:42])[N:33]2[C:34]([C:38]([OH:40])=[O:39])=[CH:35][CH2:36][S:37][C@H:32]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:15]([NH:30][CH:31]2[C:41](=[O:42])[N:33]3[C:34]([C:38]([OH:40])=[O:39])=[CH:35][CH2:36][S:37][C@H:32]23)=[O:17])[N:13]=1)=[O:7]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 540828852-(2-Formamidothiazol-4-yl)-2-(2-tert-butoxycarbonylaminoethoxyimino)acetic acid

Product 1

HCID 131712325HCID 131712325, compoundYield 60.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

N,N-Dimethylformamide (0.19 g.), phosphorylchloride (0.40 g.), 2-(2-formamidothiazol-4-yl)-2-(2-tert-butoxycarbonylaminoethoxyimino)acetic acid (syn isomer, 0.72 g.) and ethyl acetate (8.5 ml.) were treated in a similar manner to that of Example 1-(1) to give an activated acid solution. The solution was added to a solution of 7-amino-3-cephem-4-carboxylic acid (0.40 g.), trimethylsilylacetamide (1.35 g.), and bis(trimethylsilyl)acetamide (1.2 ml.) in ethyl acetate (4 ml.) at -10° C., and stirred at the same temperature for 1.5 hours. Water (10 ml.) and ethyl acetate (7 ml.) were added to the resultant solution, and the ethyl acetate layer was separated, extracted with a saturated aqueous solution of sodium bicarbonate (10 ml.). The extract was adjusted to pH 5.0 with 85% phosphoric acid and extracted with ethyl acetate (50 ml.). The extract was dried over magnesium sulfate and concentrated in vacuo to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-tertbutoxycarbonylaminoethoxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.65 g.).

Workup

  1. customto give an activated acid solution
  2. customthe ethyl acetate layer was separated
  3. extractionextracted with a saturated aqueous solution of sodium bicarbonate (10 ml.)
  4. extractionextracted with ethyl acetate (50 ml.)
  5. dry with materialThe extract was dried over magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-12a9fa768fc1420a9593357ca30403dd
Source dataset
uspto-grants-1986_07
Patent number
US04598147

Reaction notes

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