Phosphorus oxychloride → 7-[2-(2-Formamidothiazol-4-yl)-2-(2-methylthiazol-4-yl methoxyimino)acetamido]-3-cephem-4-carboxylic acid

HRID 745420Notes

Reaction equation

HRID 745420 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]2[N:17]=[C:18]([CH3:21])[S:19][CH:20]=2)[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.[NH2:27][CH:28]1[C:38](=[O:39])[N:30]2[C:31]([C:35]([OH:37])=[O:36])=[CH:32][CH2:33][S:34][C@H:29]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(OC)(=O)C.O.C(OC(=O)C)C.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]2[N:17]=[C:18]([CH3:21])[S:19][CH:20]=2)[C:10]([NH:27][CH:28]2[C:38](=[O:39])[N:30]3[C:31]([C:35]([OH:37])=[O:36])=[CH:32][CH2:33][S:34][C@H:29]23)=[O:12])[N:8]=1)=[O:2]

Participants

10

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 537187922-(2-Formamidothiazol-4-yl)-2-(2-methylthiazol-4-ylmethoxyimino)acetic acid

Product 1

HCID 1317123387-[2-(2-Formamidothiazol-4-yl)-2-(2-methylthiazol-4-yl methoxyimino)acetamido]-3-cephem-4-carboxylic acidYield 61.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6584Methyl AcetateSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Formamidothiazol-4-yl)-2-(2-methylthiazol-4-yl-methoxyimino)acetic acid (syn isomer, 0.50 g.), N,N-dimethylformamide (0.123 g.), phosphoryl chloride (0.259 g.) and ethylacetate (6 ml.) were treated in a similar manner to that of Example 1-(1) to give an activated acid solution. The solution and a solution of 7-amino-3-cephem-4-carboxylic acid (0.306 g.), trimethylsilylacetamide (1.03 g.), and bis(trimethylsilyl)acetamide (0.90 ml.) in methyl acetate (3 ml.) were treated in a similar manner to that of Example 1-(1). Water (10 ml.) was added to the resultant mixture, and the ethyl acetate layer was separated, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then evaporated in vacuo to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-methylthiazol-4-yl methoxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.48 g.)

Workup

  1. customto give an activated acid solution
  2. customthe ethyl acetate layer was separated
  3. washwashed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-768a7bc9acbc40e19fff191e7cc8578f
Source dataset
uspto-grants-1986_07
Patent number
US04598147

Reaction notes

Loading…