Reaktion #572860

Reaktionsgleichung

2,3-Dimethyl-1-phenyl-3-pyrazolin-5-one-4-carboxylic acid

triethylamine

isobutyl chloroformate

triethylamine

ampicillin

→

penicillanic acid

Ausbeute 55.9%

Lösungsmittel

dimethyl formamide

D.M.F

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigesolids were removed by filtration
2. 2
   Sonstigeat -40° C
3. 3
   Temperaturto warm to 0° C.
4. 4
   workup.STIRRINGwith stirring
5. 5
   SonstigeThe precipitate was isolated
6. 6
   Sonstigepartitioned between ethyl acetate and water
7. 7
   workup.ADDITIONThe pH was adjusted to 7.5 (bicarbonate addition)
8. 8
   Sonstigethe aqueous layer separated
9. 9
   ExtraktionExtraction with ethyl acetate
10. 10
    Sonstigedrying
11. 11
    Sonstige(Na2SO4) and evaporation

Vorschrift

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.

Quelle