Nitric Acid → 1-(2-O-nitro-3,5-di-O-acetyl-beta-D-arabinofuranosyl)-N4-acetylcytosine

HRID 1906364Notes

Reaction equation

HRID 1906364 reaction equation
C(OC(=O)C)(=O)C.[N+:8]([O-:11])([OH:10])=[O:9].[C:12]([O:15][C@@H:16]1[C@@H:20]([CH2:21][O:22][C:23](=[O:25])[CH3:24])[O:19][C@@H:18]([N:26]2[CH:36]=[CH:35][C:30]([NH:31][C:32](=[O:34])[CH3:33])=[N:29][C:27]2=[O:28])[C@H:17]1O)(=[O:14])[CH3:13]>>[N+:8]([O:11][C@H:17]1[C@H:16]([O:15][C:12](=[O:14])[CH3:13])[C@@H:20]([CH2:21][O:22][C:23](=[O:25])[CH3:24])[O:19][C@H:18]1[N:26]1[CH:36]=[CH:35][C:30]([NH:31][C:32](=[O:34])[CH3:33])=[N:29][C:27]1=[O:28])([O-:10])=[O:9]

Participants

4

Reactant 3

HCID 944Nitric AcidHCID 7918Acetic AnhydrideHCID 110791381-(3,5-di-O-acetyl-beta-D-arabinofuranosyl)-N4-acetylcytosine

Product 1

HCID 138234091-(2-O-nitro-3,5-di-O-acetyl-beta-D-arabinofuranosyl)-N4-acetylcytosineYield 86.3%

Conditions

Temperature
-30 °C

Procedure

Acetic anhydride (20 ml., 212 mmol) was added gradually to fuming nitric acid (20 ml., 477 mmol) with efficient stirring, while the temperature was kept between -30° to -35° C. by external cooling. While the mixture was being stirred vigorously, 1-(3,5-di-O-acetyl-β-D-arabinofuranosyl)-N4 -acetylcytosine (10 g., 27 mmol) was added in batches to the homogeneous mixture while maintaining the temperature at about -30° C. The clear reaction mixture was allowed to warm gradually to 0° C. After being stirred for 30 minutes at this temperature, the solution was poured into a mixture of ice and saturated aqueous (NH4)2SO4 solution (250 ml.) that was stirred until all the ice had melted. The aqueous phase was then extracted with ethyl acetate (3×250 ml). The combined extracts were washed with saturated aqueous sodium bicarbonate (2×200 ml.) and water (3×200 ml.), and was then dried (Na2SO4) Crude 1 -(2-O-nitro-3,5-di-O-acetyl-β-D-arabinofuranosyl)-N4 -acetylcytosine (10.66 g., 95%) was obtained by removing the ethyl acetate under reduced pressure. The solid residue was crystallized from ethyl acetate to obtain pure 1-(2-O-nitro-3,5-di-O-acetyl-β-D-arabinofuranosyl)-N4 -acetylcytosine (9.65 g., 86% yield): m.p. 159.7°-160.6° C.

Workup

  1. customwas kept between -30° to -35° C. by external cooling
  2. temperatureto warm gradually to 0° C
  3. stirringAfter being stirred for 30 minutes at this temperature
  4. extractionThe aqueous phase was then extracted with ethyl acetate (3×250 ml)
  5. washThe combined extracts were washed with saturated aqueous sodium bicarbonate (2×200 ml.) and water (3×200 ml.)
  6. dry with materialwas then dried (Na2SO4) Crude 1 -(2-O-nitro-3,5-di-O-acetyl-β-D-arabinofuranosyl)-N4 -acetylcytosine (10.66 g., 95%)
  7. customwas obtained
  8. customby removing the ethyl acetate under reduced pressure
  9. customThe solid residue was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-bee3f02bdb28491ead7f90e0bd9a3e70
Source dataset
uspto-grants-1987_03
Patent number
US04652554

Reaction notes

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