Trimethylsilyl triflate → 2-Chloro-5,6-dibromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)benzimidazole

HRID 727019Notes

Reaction equation

HRID 727019 reaction equation
[Cl:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([Br:11])[C:8]([Br:12])=[CH:7][C:5]=2[N:6]=1.C[Si](/N=C(/O[Si](C)(C)C)\C(F)(F)F)(C)C.C(O[C@@H:32]1[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:49])[CH3:48])[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.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>CC#N.CCOC(C)=O>[Cl:1][C:2]1[N:3]([C@@H:32]2[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:49])[CH3:48])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:33]2[O:34][C:35](=[O:37])[CH3:36])[C:4]2[CH:10]=[C:9]([Br:11])[C:8]([Br:12])=[CH:7][C:5]=2[N:6]=1

Participants

7

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 4694175,6-Dibromo-2-chloro-1H-1,3-benzodiazoleHCID 5366669trimethylsilyl (1E)-2,2,2-trifluoro-N-trimethylsilylethanimidate

Product 1

HCID 105550222-Chloro-5,6-dibromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)benzimidazoleYield 56%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 931 mg (3 mmole) of 2-chloro-5,6-dibromobenzimidazole (17) in 15 ml of dry CH3CN was treated with 0.8 mL (3 mmole) of N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA) at 75° C. for 10 min to give a clear solution. To this solution, was added 955 mg (3 mmole) of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose and 0 64 mL (3.3 mmole) of trimethylsilyl triflate (TMSTf). Stirring was continued at 75° C. for 1 hr. The reaction mixture was cooled to room temperature and then diluted with 100 mL of EtOAc. The EtOAc solution was washed with a sat. NaHCO3 solution (100 mL×2), sat. NaCl solution (100 mL), dried (Na2SO4), and evaporated. The residue was chromatographed on a silica column (3×20 cm, eluted with CHCl3). Evaporation of fractions 4-10 and recrystallization of the residue from MeOH gave 946 mg (56%) of 56 as white crystals. mp 140°-142° C.; MS m/e 565.9082 (0.9%, M+ =565.9091); 1H NMR (DMSO-d6) d 8.20 (s, 1,7-H), 8.11 (s, 1, 4-H), 6.25 (d, 1, 1'-H), 5.55 (t, 1, 2'-H), 5.43 (dd, 1, 3'-H), 4.47 (m, 2, 5'-H, 4'-H), 4.37 (m, 1, 5"-H), 2.15, 2.14, 2.02 (3×s, 3×, 3.3×Ac). Evaporation of fractions 13-15 gave 392 mg (23%) of the a anomer as a white foam. 1H NMR (DMSO-6) d 8.07, 8.06 (2×s, 2, 4-H, 7-H), 6.70 (d, 1, 1'-H), 5.71 (t, 1, 2'-H), 5.50 (dd, 1, 3 '-H), 4.81 (m. 1, 4'-H), 4. 36 (dd, 1, 5'-H), 427 (dd, 1, 5"-H).

Workup

  1. customto give a clear solution
  2. washThe EtOAc solution was washed with a sat. NaHCO3 solution (100 mL×2), sat. NaCl solution (100 mL)
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customThe residue was chromatographed on a silica column (3×20 cm, eluted with CHCl3)
  6. customEvaporation of fractions 4-10 and recrystallization of the residue from MeOH

Sources & evidence

ORD record
ord-9268a8601c6c48cd9429bd8e018f41a6
Source dataset
uspto-grants-1998_01
Patent number
US05712255

Reaction notes

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