반응 #75330

반응 방정식

(1S,3S,5R,6R) 2,2-Dimethyl-6-phenoxyacetamidopenam-3-carboxylic acid-1-oxide diphenylmethyl ester

dioxane

pyridine

acetyl bromide

→

(6R,7R) 3-Methyl-7-phenoxyacetamidoceph-3-em-4-carboxylic Acid Diphenylmethyl Ester

반응 조건

후처리

1. 1
   기타in sieve-dried
2. 2
   기타at 25° C.
3. 3
   온도the slurry was heated
4. 4
   여과filtered
5. 5
   농축concentrated in vacuo at 50° C. to a heavy oil
6. 6
   여과filtered
7. 7
   농축concentrated in vacuo to dryness
8. 8
   workup.DISSOLUTIONThe residue was dissolved in hot 1-butanol (500 mls, ca. 90°-95° C.)
9. 9
   온도to cool to 25° C
10. 10
    온도The slurry was cooled to 0°-5° C. for 16 hours
11. 11
    여과filtered
12. 12
    세척washed with cold butanol (0° -5° C., 100 mls)
13. 13
    건조with Skellysolve B (200 mls), and oven-dried at 45° C. to constant weight

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-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:

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