Ethyl Acetate → HCID 86590823, compound

HRID 660004Notes

Reaction equation

HRID 660004 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:13]2[O:14][CH2:15][C@@:10]1([CH2:27][O:28]S(C)(=O)=O)[O:11][C@H:12]2[N:16]1[CH:24]=[N:23][C:22]2[C:17]1=[N:18][C:19]([NH2:26])=[N:20][C:21]=2[Cl:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33](O[Na])([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:34].CCOC(C)=O.C([O-])(O)=O.[Na+]>CS(C)=O.[Cl-].[Na+].O>[CH2:1]([O:8][C@@H:9]1[C@@H:13]2[O:14][CH2:15][C@@:10]1([CH2:27][O:28][C:33](=[O:34])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[O:11][C@H:12]2[N:16]1[CH:24]=[N:23][C:22]2[C:17]1=[N:18][C:19]([NH2:26])=[N:20][C:21]=2[Cl:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 86590824HCID 86590824, compoundHCID 178526065HCID 178526065, compound

Product 1

HCID 86590823HCID 86590823, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

Compound 84 (4.49 g, 9.32 mmol) was dissolved in DMSO (200 mL) and BzONa (6.76 g, 46.6 mmol) was added. The reaction was stirred at 100° C. for 16 h. The reaction allowed to cool to room temperature and EtOAc (200 mL) and brine:sat. aq NaHCO3 (1:1, 400 mL) was added. The mixture was transferred to a separatory funnel. The phases were separated and the aq-phase was extracted with EtOAc (3×200 mL). The combined organic phase was washed with brine (half-sat., 2×200 mL), dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by DCVC (Ø=6 cm, 50-100% EtOAc in n-heptane v/v, 5% increments, 2×100 mL fractions, 0-10% MeOH in EtOAc v/v, 1% increments, 100 mL) yielding nucleoside 85 (3.30 g, 70%) as a white powder. Rf=0.40 (35% n-heptane in EtOAc (v/v)). ESI-MS m/z found 508.2.; 510.1 ([MH]+, calcd. 508.1). 1H NMR (DMSO-d6, 400 MHz): δ 8.05 (s, 1H, H8), 7.98 (d, 2H, J=7.3 Hz, Bz), 7.68 (t, 1H, J=7.3 Hz, Bz), 7.53 (t, 2H, J=7.7 Hz, Bz), 7.25-7.15 (m, 3H, Bn), 7.05-7.00 (m, 4H, Bn, NH2), 5.98 (s, 1H, H1′), 4.85 (s, 2H, H5″), 4.67 (d, 1H, J=1.8 Hz, H2′), 4.50 (d, 1H, J=12.1 Hz, CH2), 4.35 (d, 1H, J=2.0 Hz, H3′), 4.34 (d, 1H, J=11.7 Hz, CH2), 4.16 (d, 1H, J=8.4 Hz, CH2), 3.98 (d, 1H, J=8.1 Hz, CH2). 13C NMR (DMSO-d6, 100 MHz): δ 165.1 (PhCO), 159.6, 152.9, 149.0 (C2, C4, C6), 140.6 (C8), 136.7, 133.5, 129.2, 128.9, 128.7, 128.0, 127.9, 127.7, 127.6 (Ph), 123.2 (C5), 86.7 (C4′), 85.9 (C1′), 79.9 (C3′), 75.8 (C2′), 72.5, 72.1 (5′, CH2Ph), 60.4 (C5″).

Workup

  1. temperatureto cool to room temperature
  2. customThe mixture was transferred to a separatory funnel
  3. customThe phases were separated
  4. extractionthe aq-phase was extracted with EtOAc (3×200 mL)
  5. washThe combined organic phase was washed with brine (half-sat., 2×200 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by DCVC (Ø=6 cm, 50-100% EtOAc in n-heptane v/v, 5% increments, 2×100 mL fractions, 0-10% MeOH in EtOAc v/v, 1% increments, 100 mL)

Sources & evidence

ORD record
ord-bce96789376542b8aee2513c01e64528
Source dataset
uspto-grants-2011_12
Patent number
US08084458B2

Reaction notes

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