Acetamide → 2-Bromo-5,6-dichloro-1-(5-deoxy-2,3-di-O-acetyl-beta-D-ribofuranosyl)benzimidazole

HRID 2227170Notes

Reaction equation

HRID 2227170 reaction equation
[Br:1][C:2]1[NH:6][C:5]2[CH:7]=[C:8]([Cl:12])[C:9]([Cl:11])=[CH:10][C:4]=2[N:3]=1.C(N)(=O)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(O[CH:33]1[O:45][C@H:44]([CH3:46])[C@@H:39]([O:40][C:41](=[O:43])[CH3:42])[C@H:34]1[O:35][C:36](=[O:38])[CH3:37])(=O)C.C(=O)(O)[O-].[Na+]>C(#N)C.C(Cl)Cl>[Br:1][C:2]1[N:3]([C@@H:33]2[O:45][C@H:44]([CH3:46])[C@@H:39]([O:40][C:41](=[O:43])[CH3:42])[C@H:34]2[O:35][C:36](=[O:38])[CH3:37])[C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1

Participants

8

Reactant 5

HCID 178AcetamideHCID 65367Trimethylsilyl triflateHCID 4660172-bromo-5,6-dichloro-1H-benzimidazoleHCID 516892Sodium BicarbonateHCID 11196237Tri-O-acetyl-5-deoxy-D-ribofuranose

Product 1

HCID 699962602-Bromo-5,6-dichloro-1-(5-deoxy-2,3-di-O-acetyl-beta-D-ribofuranosyl)benzimidazoleYield 78%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

2-Bromo-5,6-dichloro-1H-benzimidazole (5.11 g, 19.21 mmol), and N,O-bis(trimethylsiyl) acetamide (Aldrich, 4.81 mL, 19.21 mmol) were combined with acetonitrile (Aldrich Sure Seal, 100 mL) and refluxed under nitrogen for 3 h. The solution was cooled to rt and trimethylsilyl triflate (Aldrich, 7.70 mL, 38.42 mmol) was added. After 15 min, 5-deoxy-1,2,3-tri-O-acetyl-D-ribofuranose (5.0 g, 19.21 mmol) in acetonitrile (4 mL) was added. The solution was stirred under nitrogen at rt for 3.5 h, then poured into 10% aqueous sodium bicarbonate (300 mL) and extracted with ethyl acetate (3×100 mL). The organic layers were washed with water (1×100 mL), dried with magnesium sulfate (anhyd), filtered, and evaporated. The crude residue was purified on a silica gel column with 1:30 acetone:CH2Cl2 to give the title compound (6.96 g, 14.93 mmol, 78%); MS (El): m/z (rel. intensity) 489 (0.22, M++Na); 1H NMR (DMSO-d6) δ8.13 (s, 1H, Ar—H), 8.02 (s, 1H, Ar—H), 6.17 (d, 1H, CH, J=6.6 Hz), 5.67 (t, 1H, CH, J=13.9 Hz), 5.29 (t, 1H, CH, J=7.2 Hz), 4.28 (m, 1H, CH), 2.16 (s, 3H, OAc), 2.04 (s, 3H, OAc), 1.53 (d, 3H, CH3, J=6.5 Hz).

Workup

  1. temperaturerefluxed under nitrogen for 3 h
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe organic layers were washed with water (1×100 mL)
  4. dry with materialdried with magnesium sulfate (anhyd)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude residue was purified on a silica gel column with 1:30 acetone

Sources & evidence

ORD record
ord-007caf17679d4d64b7f286bac5c4be2b
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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