Ampicillin → Penicillanic Acid

HRID 485678

Reaction equation

HRID 485678 reaction equation
CN1C(C)=C(C(O)=O)C(=O)N1C1C=CC=CC=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[CH3:33][C:34]1([CH3:56])[S:38][C@@H:37]2[C@H:39](NC([C@H](N)C3C=CC=CC=3)=O)[C:40](=[O:41])[N:36]2[C@H:35]1[C:53]([OH:55])=[O:54]>CN(C)C=O.CCOCC>[CH3:33][C:34]1([CH3:56])[S:38][C@@H:37]2[CH2:39][C:40](=[O:41])[N:36]2[C@H:35]1[C:53]([OH:55])=[O:54]

Participants

7

Reactant 4

HCID 6249AmpicillinHCID 8471Triethylamine2×HCID 62365Isobutyl chloroformateHCID 246564Antipyric acid

Product 1

HCID 6891Penicillanic AcidYield 55.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-10 °C

Procedure

2,3-Dimethyl-1-phenyl-3-pyrazolin-5-one-4-carboxylic acid (0.186 g, 0.8 mmol) in dry dimethyl formamide (D.M.F) (4 ml) was treated with triethylamine (0.12 ml, 0.8 mmol). The solution was cooled to -10° C. and isobutyl chloroformate (0.10 ml, 0.76 mmol) added dropwise. After 1 hour at -10° C., solids were removed by filtration and the solution added to ampicillin (anhydrous) (0.28 g, 0.8 mmol) premixed with triethylamine (0.12 ml, 0.8 mmol) in D.M.F. (10 ml) at -40° C. The solution was allowed to warm to 0° C., stirred for 90 minutes and poured into excess dry ether, with stirring. The precipitate was isolated and partitioned between ethyl acetate and water. The pH was adjusted to 7.5 (bicarbonate addition); the aqueous layer separated and acidified to pH 1.5 (HCl(5N)). Extraction with ethyl acetate, drying (Na2SO4) and evaporation gave the title product as the free penicillanic acid (0.09 g, 20%), δ((CD3)2CO) 1.50, 1.58 (2×3H, 2s, (CH3)2), 2.68 (3H, s,=C--CH3), 3.34 (3H, s, --NCH3), 4.36 (1H, s, C3 -proton), 5.53 (1H, d, J 4 Hz, C5 -proton), 5.71 (1H, d of d, J 4, 8 Hz, C6 -proton), 5.94 (1H, d, J 8 Hz, --CHCON--), 7.53 (10H, complex, aryl protons), 8.20 (1H, d, J 8 Hz, --NH--), 9.78 (1H, d, J 8 Hz, --NH--), 6.5-9 (1H, br, --CO2H). The free acid was converted to the sodium salt by addition, to an acetone solution of the free acid, of a solution of sodium ethylhexanoate (0.084 ml, 1.9N) in methyl isobutyl ketone, further addition of ether, and filtration of the precipitate. The sodium salt (2) showed vmax (nujol) 1780, 1760, 1690, 1655, 1600 cm-1.

Workup

  1. customsolids were removed by filtration
  2. customat -40° C
  3. temperatureto warm to 0° C.
  4. stirringwith stirring
  5. customThe precipitate was isolated
  6. custompartitioned between ethyl acetate and water
  7. additionThe pH was adjusted to 7.5 (bicarbonate addition)
  8. customthe aqueous layer separated
  9. extractionExtraction with ethyl acetate
  10. customdrying
  11. custom(Na2SO4) and evaporation

Sources & evidence

ORD record
ord-5451ab24690f429da35d2578941461af
Source dataset
uspto-grants-1985_08
Patent number
US04537886

Linked notes

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