Acetamide → HCID 69946643, compound

HRID 1281671Notes

Reaction equation

HRID 1281671 reaction equation
[Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]2[N:6]=[CH:7][NH:8][C:4]=2[CH:3]=1.C(N)(=O)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(O[C@@H:32]1[O:49][CH2:48][C@@H:43]([O:44][C:45](=[O:47])[CH3:46])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:33]1[O:34][C:35](=[O:37])[CH3:36])(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]2[N:6]([C@@H:48]3[O:49][CH2:32][C@@H:33]([O:34][C:35](=[O:37])[CH3:36])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:43]3[O:44][C:45](=[O:47])[CH3:46])[CH:7]=[N:8][C:4]=2[CH:3]=1

Participants

7

Reactant 5

HCID 178AcetamideHCID 65367Trimethylsilyl triflateHCID 97336β-D-Ribopyranose, 1,2,3,4-tetraacetateHCID 516892Sodium BicarbonateHCID 178422326HCID 178422326, compound

Product 1

HCID 69946643HCID 69946643, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

As described in General Procedure III, 5-chloro-6methylbenzimidazole (1.0 g, 6 mmol), N,O-bis(trimethylsiyl) acetamide (Aldrich, 1.3 ml, 5.2 mmol), and 1,2-dichloroethane (Aldrich Sure Seal, 300 mL) were combined and refluxed under nitrogen for 0.5 h. The solution was cooled to room temperature and trimethylsilyl triflate (Aldrich, 1.3 ml, 6.7 mmol) was added. Immediately, 2.0 g (6.3 mmol) solid 1,2,3,4-tetra-O-acetyl-b-D-ribopyranose (beta-D-ribopyranose 1,2,3,4-tetraacetate, Aldrich, Milwaukee) was added. The solution was stirred under nitrogen at reflux overnight, then poured into 7% aqueous sodium bicarbonate and extracted with chloroform. The organic layer was dried with magnesium sulfate (anhyd), filtered, and evaporated. The crude residue was purified on a silica gel column (5×20 cm, 230-400 mesh) eluting with a step gradient of 0.25 to 2.5% methanol in chloroform to give 0.07 g (0.16 mmol) 5-Chloro-6-methyl-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole; MS (AP+): m/z (rel. intensity) 447 (1.0, M+23 (Na)) 1H NMR (DMSO-d6) δ8.36 (s,1H), 7.90 (s, 1H), 7.68 (s, 1H), 5.97-5.95 (d, 1H, J=9.1 Hz), 5.72-5.69 (m, 2H), 5.41-5.40 (m, 1H), 4.02-3.92 (m, 2H), 2.42 (s, 3H), 2.20 (s, 3H), 1.98 (s, 3H), 1.69 (s, 3H) and 0.090 g (0.21 mmol) 6-Chloro-5-methyl-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole 1H NMR (DMSO-d6) δ8.36 (s,1H), 8.06 (s, 1H), 7.60 (s, 1H), 5.99-5.96 (d, 1H, J=9.6 Hz), 5.73-5.66 (m, 2H), 5.45-5.40 (m, 1H), 4.02-3.92 (m, 2H), 2.37 (s, 3H), 2.20 (s, 3H), 1.98 (s, 3H), 1.69 (s, 3H) and 0.13 g (0.31 mmol) of a mixture of the two regioisomers (11% total yield).

Workup

  1. temperaturerefluxed under nitrogen for 0.5 h
  2. temperatureat reflux overnight
  3. extractionextracted with chloroform
  4. dry with materialThe organic layer was dried with magnesium sulfate (anhyd)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude residue was purified on a silica gel column (5×20 cm, 230-400 mesh)
  8. washeluting with a step gradient of 0.25 to 2.5% methanol in chloroform

Sources & evidence

ORD record
ord-d5114685ac89480fa3413e8f0b8fd8a3
Source dataset
uspto-grants-2002_09
Patent number
US06455507B1

Reaction notes

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