Uracil → 1-(2-O-Acetyl-4-C-acetoxymethyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)uracil

HRID 1663531Notes

Reaction equation

HRID 1663531 reaction equation
[C:1]([O:4][CH2:5][C@:6]1([CH2:27][O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:14][CH:9](OC(=O)C)[C@H:8]([O:15][C:16](=[O:18])[CH3:17])[C@@H:7]1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2].[NH:36]1[CH:43]=[CH:42][C:40](=[O:41])[NH:39][C:37]1=[O:38].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>C(#N)C>[C:16]([O:15][C@@H:8]1[C@H:7]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@@:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])([CH2:27][O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[O:14][C@H:9]1[N:36]1[CH:43]=[CH:42][C:40](=[O:41])[NH:39][C:37]1=[O:38])(=[O:18])[CH3:17]

Participants

6

Reactant 4

HCID 1174UracilHCID 65367Trimethylsilyl triflateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 153742654-C-(Acetoxymethyl)-1,2-di-O-acetyl-3,5-di-O-benzyl-D-ribofuranose

Product 1

HCID 206107821-(2-O-Acetyl-4-C-acetoxymethyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)uracil

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of the anomeric mixture 33 (3.0 g, 6.17 mmol) and uracil (1.04 g, 9.26 mmol) in anhydrous acetonitrile (65 cm3) was added N,O-bis(trimethylsilyl)acetamide (9.16 cm3, 37.0 mmol). The reaction mixture was stirred for 1 h at room temperature and cooled to 0° C. Trimethylsilyl triflate (1.8 cm3, 10.0 mmol) was added dropwise and the solution was stirred at 60° C. for 2 h. The reaction was quenched by addition of a saturated aqueous solution of sodium hydrogencarbonate (10 cm3) at 0° C. and extraction was performed with dichloromethane (3×20 cm3). The combined organic phase was washed with brine (2×20 cm3) and was dried (Na2SO4). The solvents were removed under reduced pressure and the residue was purified by silica gel column chromatography using dichloromethane/methanol (99:1, v/v) as eluent to give nucleoside 40 as a white solid material (2.5 g, 75%). δH (CDCl3) 9.57 (1H, br s, NH), 7.63 (1H, d, J 8.2, 6-H), 7.40-7.24 (10H, m, Bn), 6.18 (1H, d, J 4.5, 1′-H), 5.39-5.32 (2H, m, 2′-H, 5-H), 4.61 (1H, d, J 11.6, Bn), 4.49-4.40 (5H, m, 3′-H, Bn, 1″-Ha), 4.37 (1H, d, J 12.3, 1″-Hb), 3.76 (1H, d, J 10.1, 5-Ha), 3.49 (1H, d, J 10.1, 5′-Hb), 2.09 (s, 3H, COCH3), 2.04 (3H, s, COCH3). δc (CDCl3) 170.47, 169.94 (C═O), 163.32 (C-4), 150.30 (C-2), 140.24 (C-6), 137.15, 136.95, 128.65, 128.52, 128.32, 128.19, 128.02, 127.77 (Bn), 102.57 (C-5), 87.41, 86.14 (C-1′, C-4′), 77.09, 74.84, 74.51, 73.75, 70.60, 63.73 (C-2′, C-3′, C-5′, C-1″, Bn), 20.79, 20.68 (COCH3). FAB-MS m/z 539 [M]+.

Workup

  1. temperaturecooled to 0° C
  2. stirringthe solution was stirred at 60° C. for 2 h
  3. customThe reaction was quenched by addition of a saturated aqueous solution of sodium hydrogencarbonate (10 cm3) at 0° C.
  4. extractionextraction
  5. washThe combined organic phase was washed with brine (2×20 cm3)
  6. dry with materialwas dried (Na2SO4)
  7. customThe solvents were removed under reduced pressure
  8. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8ca7036b053f4b9f88e196c2b21c07b7
Source dataset
uspto-grants-2011_10
Patent number
US08034909B2

Reaction notes

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