Hydrochloric Acid → 1(3,5-Di-O-benzyl-4-C-hydroxymethyl-beta-D-ribofuranosyl)uracil

HRID 1797362Notes

Reaction equation

HRID 1797362 reaction equation
C([O:4][C@@H:5]1[C@H:9]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@@:8]([CH2:27][O:28]C(=O)C)([CH2:18][O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:7][C@H:6]1[N:32]1[CH:39]=[CH:38][C:36](=[O:37])[NH:35][C:33]1=[O:34])(=O)C.C[O-].[Na+].Cl>CO>[CH2:11]([O:10][C@@H:9]1[C@@:8]([CH2:27][OH:28])([CH2:18][O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:7][C@@H:6]([N:32]2[CH:39]=[CH:38][C:36](=[O:37])[NH:35][C:33]2=[O:34])[C@@H:5]1[OH:4])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 206107821-(2-O-Acetyl-4-C-acetoxymethyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)uracil

Product 1

HCID 542980801(3,5-Di-O-benzyl-4-C-hydroxymethyl-beta-D-ribofuranosyl)uracil

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of nucleoside 40 (2.0 g, 3.7 mmol) in methanol (25 cm3) was added sodium methoxide (0.864 g, 95%, 16.0 mmol). The reaction mixture was stirred at room temperature for 10 min and neutralised with 20% aqueous hydrochloric acid. The solvent was partly evaporated and the residue was extracted with ethyl acetate (3×50 cm3). The combined organic phase was washed with a saturated aqueous solution of sodium hydrogencarbonate (3×20 cm3) and was dried (Na2SO4). The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography using dichloromethane/methanol (98.5:1.5, v/v) as eluent to give 41 as a white solid material (1.58 g, 95%). δH (CDCl3) 9.95 (1H, br s, NH), 7.69 (d, J 8.1, 6-H), 7.35-7.17 (10H, m, Bn), 6.02 (1H, d, J 2.3, 1′-H), 5.26 (1H, d, J 8.1, 5-H), 4.80 (1H, d, J 11.7, Bn), 4.47 (1H, d, J 11.7, Bn), 4.45-4.24 (4H, m, Bn, 2′-H, 3′-H), 3.81 (1H, d, J 11.9, 1″-Ha), 3.69 (2H, br s, 2′-OH, 1″-OH), 3.67 (2H, m, 5′-Ha, 1″-Hb), 3.48 (1H, d, J 10.3, 5′-Hb). δC (CDCl3) 163.78 (C-4), 150.94 (C-2), 140.61 (C-6), 137.33, 137.22, 128.59, 128.18, 128.01 (Bn), 102.16 (C-5), 91.46, 88.36 (C-1′, C-4′), 76.73, 74.66, 73.71, 73.29, 70.81, 62.81 (C-2′, C-3′, C-5′, C-1″, Bn). FAB-MS m/z 455 [M+H]+.

Workup

  1. customThe solvent was partly evaporated
  2. extractionthe residue was extracted with ethyl acetate (3×50 cm3)
  3. washThe combined organic phase was washed with a saturated aqueous solution of sodium hydrogencarbonate (3×20 cm3)
  4. dry with materialwas dried (Na2SO4)
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0f752e25b0d24abd92c9cdbf2bd919f9
Source dataset
uspto-grants-2006_04
Patent number
US07034133B2

Reaction notes

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