beta-D-Ribofuranose, 1-acetate 2,3,5-tribenzoate → (2R,3S,4R,5R)-2-(hydroxymethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol

HRID 6345

Reaction equation

HRID 6345 reaction equation
[Cl:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1.FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.[Si](S(C(F)(F)F)(=O)=O)(C)(C)C.C(O[C@@H:43]1[O:65][C@H:64]([CH2:66][O:67]C(=O)C2C=CC=CC=2)[C@@H:54]([O:55]C(=O)C2C=CC=CC=2)[C@H:44]1[O:45]C(=O)C1C=CC=CC=1)(=O)C>C(#N)C>[Cl:1][C:2]1[N:3]([C@@H:43]2[O:65][C@H:64]([CH2:66][OH:67])[C@@H:54]([OH:55])[C@H:44]2[OH:45])[C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1

Participants

6

Reactant 4

HCID 81455beta-D-Ribofuranose, 1-acetate 2,3,5-tribenzoateHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 2860092,5,6-Trichloro-1H-benzimidazoleHCID 13257444Trifluoromethyl(trimethylsilyl) sulfone

Product 1

HCID 465095(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

2,5,6-Trichlorobenzimidazole (700 mg, 0.0032 moles) was dissolved in acetonitrile and BSTFA (1 ml, 0.0038 moles) was added. The mixture was heated at 75° C. for 20 minutes. TMSTf (1 ml, 0.0051 moles) and 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (1.9 g, 0.0038 moles) were added while heating was continued for 45 min. The acetonitrile was removed under reduced pressure and the protected nucleoside was separated on a silica column, eluting with chloroform. The benzoyl protecting groups were removed by overnight treatment at room temperature with methanolic ammonia. The nucleoside was separated on a column using 50% EtOAc/hexane and then 10% MeOH/CHCl3. The isolated compound was recrystallized from methanol. Yield: (74%); MP: 185°-186° C.; TLC (10% MeOH/CHCl3): Rf=0.20; 1H NMR (DMSO-d6) δ3.68 ppm (q, 2H), 4.00 (d, 1H), 4.12 (t, 1H), 4.40 (q, 1H), 5.28 (d, 1H), 5.41 (t, 1H), 5.49 (d, 1H), 5.57 (d, 1H), 7.96 (s, 1H), 8.55 (s, 1H); 13C NMR (DMSO-d6, Broad band decoupling): d 61.08 ppm, 69.80, 71.70, 86.47, 89.16, 114.93, 120.04, 125.77, 125.97, 132.30, 140.96, 142.16; MS (Fast Atom Bombardment): m/e (M+ 6) 359, (M+ 4) 357, (M+ 2) 355, (M+) 353, 319, 285, 263, 221, 187, 177, 133, 115, 103, 97, 85.

Workup

  1. temperaturewhile heating
  2. customThe acetonitrile was removed under reduced pressure
  3. customthe protected nucleoside was separated on a silica column
  4. washeluting with chloroform
  5. customThe benzoyl protecting groups were removed by overnight treatment at room temperature with methanolic ammonia
  6. customThe nucleoside was separated on a column
  7. customThe isolated compound was recrystallized from methanol

Sources & evidence

ORD record
ord-2ecad7da38b24e3d9a065c9be68c87c0
Source dataset
uspto-grants-1993_09
Patent number
US05248672

Linked notes

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