Thymine → 1-(4-C-(Acetoxymethyl)-2-O-acetyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)thymine

HRID 2100266Notes

Reaction equation

HRID 2100266 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:44]=[C:42]([CH3:43])[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: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][C@@H:9]([N:36]2[CH:44]=[C:42]([CH3:43])[C:40](=[O:41])[NH:39][C:37]2=[O:38])[C@H:8]([O:15][C:16](=[O:18])[CH3:17])[C@@H:7]1[O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 1135ThymineHCID 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 153742661-(4-C-(Acetoxymethyl)-2-O-acetyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)thymine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the anomeric mixture 33 (736 mg, 1.51 mmol) and thymine (381 mg, 3.03 mmol) in anhydrous acetonitrile (14.5 cm3) was added N,O-bis(trimethylsilyl)acetamide (2.61 cm3, 10.6 mmol). The reaction mixture was stirred at reflux for 1 h, then cooled to 0° C. Trimethylsilyl triflate (0.47 cm3, 2.56 mmol) was added dropwise under stirring and the solution was stirred at 65° C. for 2 h. The reaction was quenched with a cold saturated aqueous solution of sodium hydrogen carbonate (15 cm3) and extraction was performed with dichloromethane (3×10 cm3). The combined organic phase was washed with saturated aqueous solutions of sodium hydrogen-carbonate (2×10 cm3) and brine (2×10 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 (98:2, v/v) as eluent to give nucleoside 34 as a white solid material (639 mg, 76%). δH (CDCl3) 8.98 (1 H, br-s, NH), 7.39-7.26 (11 H, m, Bn, 6-H), 6.22 (1 H, d, J 5.3, 1′-H), 5.42 (1 H, t, J 5.4, 2′-H), 4.63-4.43 (5H, m, 3′-H, Bn), 4.41 (1 H, d, J 12.2, 5′-Ha), 4.17 (1H, d, J 12.1, 5′-Hb), 3.76 (1 H, d, J 10.2, 1-″H), 3.51 (1 H, d, J 10.4, 1″-Hb), 2.09 (3 H, s, COCH3), 2.03 (3 H, s, COCH3), 1.53 (3 H, d, J 0.9, CH3). δC (CDCl3) 170.8, 170.4 (C═O), 163.9 (C-4), 150.6 (C-2), 137.4 (C-6) 137.4, 136.1, 128.9, 128.8, 128.4, 128.2, 127.9 (Bn), 111.7 (C-5), 87.2, 87.2, 86.1 (C-1′, C-3′, C-4′), 77.6 (C-2′), 74.8, 73.9, 71.1, 63.8 (Bn, C-1″, C-5′), 20.9, 20.8 (COCH3), 12.0 (CH3). FAB-MS m/z 553 [M+H]+. Found: C, 62.7; H, 5.9; N, 4.7; C29H32N2O9 requires C, 63.0; H, 5.8; N, 5.1%.

Workup

  1. temperatureat reflux for 1 h
  2. stirringunder stirring
  3. stirringthe solution was stirred at 65° C. for 2 h
  4. customThe reaction was quenched with a cold saturated aqueous solution of sodium hydrogen carbonate (15 cm3) and extraction
  5. washThe combined organic phase was washed with saturated aqueous solutions of sodium hydrogen-carbonate (2×10 cm3) and brine (2×10 cm3)
  6. dry with materialwas dried (Na2SO4)
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-56a984d9750c4e3d9eba5f88571fcf42
Source dataset
uspto-grants-2009_08
Patent number
US07572582B2

Reaction notes

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