Phosphoric Acid → HCID 15670703, compound

HRID 345632Notes

Reaction equation

HRID 345632 reaction equation
C(O)(=O)C(O)=O.[O:7]=[C:8]1[N:11]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH2:10][CH2:9]1.[NH4+].[OH-].P(=O)(O)(O)O.[C:24]1([CH2:30][C:31]([O:33]C)=O)C=C[CH:27]=[CH:26][CH:25]=1.CC1(C)S[C@@H]2[C@H]([NH:44][C:45]([CH2:47][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[O:46])C(=O)N2[C@H]1C(O)=O>O>[C:48]1([CH2:47][C:45]([NH:44][C@@H:9]2[C:8](=[O:7])[N:11]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[C@@H:10]2[CH2:27][CH2:26][C:25]2[O:33][CH:31]=[CH:30][CH:24]=2)=[O:46])[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

7

Reactant 5

HCID 1004Phosphoric AcidHCID 5904Penicillin GHCID 7559Methyl phenylacetateHCID 14923Ammonium Hydroxide2×HCID 86745172HCID 86745172, compound

Product 1

HCID 15670703HCID 15670703, compoundYield 41.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
28 °C

Procedure

A 4.00 gram sample (11.7 mmoles) of cis(racemic at 2 and 3 position) 3-amino-2-2-(2-furanyl)ethyl]-4-oxo-1-azetidine acetic acid, methyl ester oxalate was dissolved in 40 ml. of deionized water by adjusting the pH to 7.0 with concentrated NH4OH. After readjusting the pH to 6.0 with phosphoric acid, 1.41 grams (9.36 mmoles) of methyl phenylacetate was added and the temperature was maintained at 28° C. Milli-Q water washed Sclavo penicillin G amidase (84 I.U./gram of substrate; 7.18 I.U./mmole of substrate) was added and the reaction was allowed to proceed for four hours. The pH of the reaction was maintained at 6.0 by the addition of 2.5 N NH4OH. The reaction mixture was then filtered through a ground glass filter and the beads were washed successively with methylene chloride and water to remove product. The filtrate and washes were combined and the aqueous layer was extracted several times with methylene chloride. The extract was dried with anhydrous sodium sulfate and evaporated to dryness in vacuo. The residue, which contained 1.78 grams (41.1% yield) of title compound, was purified by semi-preparative HPLC using Waters RCM 25×10 column containing two cartridges of prep Nova-Pak HRC18 with one prep guard Nova-Pak HRC18 eluted with 0.2% trifluoroacetic acid in water/acetonitrile (70/30), to obtain 1.25 grams (28.8% yield) of the title compound.

Workup

  1. additionwas added
  2. filtrationThe reaction mixture was then filtered through a ground glass
  3. filtrationfilter
  4. washthe beads were washed successively with methylene chloride and water
  5. customto remove product
  6. extractionthe aqueous layer was extracted several times with methylene chloride
  7. dry with materialThe extract was dried with anhydrous sodium sulfate
  8. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-f06771adf0d04069a9228e8677a11138
Source dataset
uspto-grants-1991_10
Patent number
US05057607

Reaction notes

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