反応 #75330

反応方程式

(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

反応条件

後処理

1. 1
   その他in sieve-dried
2. 2
   その他at 25° C.
3. 3
   温度the slurry was heated
4. 4
   ろ過filtered
5. 5
   濃縮concentrated in vacuo at 50° C. to a heavy oil
6. 6
   ろ過filtered
7. 7
   濃縮concentrated in vacuo to dryness
8. 8
   workup.DISSOLUTIONThe residue was dissolved in hot 1-butanol (500 mls, ca. 90°-95° C.)
9. 9
   温度to cool to 25° C
10. 10
    温度The slurry was cooled to 0°-5° C. for 16 hours
11. 11
    ろ過filtered
12. 12
    洗浄washed with cold butanol (0° -5° C., 100 mls)
13. 13
    乾燥with Skellysolve B (200 mls), and oven-dried at 45° C. to constant weight

実験手順

(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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