Ampicillin → Penicillanic Acid

HRID 485678

반응식

HRID 485678 반응식
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]

참가 물질

7

반응물 4

HCID 6249AmpicillinHCID 8471Triethylamine2회HCID 62365Isobutyl chloroformateHCID 246564Antipyric acid

생성물 1

HCID 6891Penicillanic Acid수율 55.9%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매2회

반응 조건

온도
-10 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5451ab24690f429da35d2578941461af
출처 데이터셋
uspto-grants-1985_08
특허 번호
US04537886

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