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 1105784

반응식

HRID 1105784 반응식
[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

참가 물질

5

반응물 4

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

생성물 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

반응 조건

온도
100 °C

실험 절차

(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-drived, 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:

후처리

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

출처 및 근거

ORD 기록
ord-591e7dc3271a4529b8c755f9505db6d1
출처 데이터셋
uspto-grants-1982_01
특허 번호
US04310459

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