Pyridine → benzhydryl (6R,7R)-3-methyl-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 2059147

Reaktionsgleichung

Reaktionsgleichung von HRID 2059147
[C:1]1([CH:7]([O:14][C:15]([C@@H:17]2[N:21]3[C:22](=[O:35])[C@@H:23]([NH:24]C(=O)COC4C=CC=CC=4)[C@H:20]3[S@@:19](=O)[C:18]2([CH3:38])[CH3:37])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=[CH:43][CH:42]=[CH:41][CH:40]=1.C(Br)(=O)C.[O:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>>[C:8]1([CH:7]([O:14][C:15]([C:17]2[N:21]3[C:22](=[O:35])[C@@H:23]([NH:24][C:54](=[O:49])[CH2:53][O:52][C:51]4[CH:50]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C@H:20]3[S:19][CH2:37][C:18]=2[CH3:38])=[O:16])[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Komponenten

5

Edukt 4

HCID 1049PyridineHCID 10482Acetyl bromideHCID 312751,4-DioxaneHCID 56631626Benzhydryl penicillin V sulfoxide, (S)-

Produkt 1

HCID 112091benzhydryl (6R,7R)-3-methyl-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(1S,3S,5R,6R) 2,2-Dimethyl-6-phenoxyacetamidopenam-3-carboxylic acid-1-oxide diphenylmethyl ester (25.00 gms, 45.41 mmoles) was dissolved in sieve-dried, peroxide-free dioxane (250 mls) at 25° C. with good agitation. To this solution, in order, were added pyridine (10.99 mls, 10.78 gms, 136.22 mmoles), acetyl bromide (0.67 mls, 1.12 gms, 9.08 mmoles) and dimethylsilyl diisocyanate (16.14 gms, 113.51 mmoles), and the slurry was heated to reflux (ca. 100° C.) for 4 hours. The dioxane slurry was then cooled to 25° C., filtered, and concentrated in vacuo at 50° C. to a heavy oil. The oil was taken up in methylene chloride (400 mls), stirred for 15 minutes at 25° C., filtered, and concentrated in vacuo to dryness. The residue was dissolved in hot 1-butanol (500 mls, ca. 90°-95° C.) and allowed to cool to 25° C. The slurry was cooled to 0°-5° C. for 16 hours, filtered, washed with cold butanol (0°-5° C., 100 mls), then with Skellysolve B (200 mls), and oven-dried at 45° C. to constant weight. Yield: 20.2 gms, 86.4% of snow-white crystalline title compound. The NMR spectrum was clean and consistent for the desired structure, as follows: 80 MHz H' NMR, δ(CD2Cl2) 2.08 (3H, s, CH3), 3.04-3.62 (2H, m, CH2, JAB =18.1 Hz), 4.55 (2H, s, CH2), 4.99-5.05 (1H, d, β-lactam H, JA =4.7 Hz), 5.74-5.91 (1H, m, β-lactam H, J=4.7 Hz), 6.75-7.50 (17H, m, aromatic CH, and NH).

Aufarbeitung

  1. customin sieve-dried
  2. customat 25° C.
  3. temperaturethe slurry was heated
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo at 50° C. to a heavy oil
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to dryness
  8. dissolutionThe residue was dissolved in hot 1-butanol (500 mls, ca. 90°-95° C.)
  9. temperatureto cool to 25° C
  10. temperatureThe slurry was cooled to 0°-5° C. for 16 hours
  11. filtrationfiltered
  12. washwashed with cold butanol (0°-5° C., 100 mls)
  13. dry with materialwith Skellysolve B (200 mls), and oven-dried at 45° C. to constant weight

Quellen und Nachweise

ORD-Eintrag
ord-8b1fbf34af2448ad8f54e9bac44e10af
Quelldatensatz
uspto-grants-1982_03
Patentnummer
US04322347

Verknüpfte Notizen

Wird geladen…