Trimethylsilyl triflate → 1-(2,3,5-Tri-O-benzyl-beta-D-ribofuranosyl)-2,4,5,6-tetrachlorobenzimidazole

HRID 727029Notes

Reaction equation

HRID 727029 reaction equation
[N+](C1C=CC(C(O[C@@H:11]2[O:31][C@H:30]([CH2:32][O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C@@H:21]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:12]2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=O)=CC=1)([O-])=O.[Cl:43][C:44]1[NH:45][C:46]2[C:52]([Cl:53])=[C:51]([Cl:54])[C:50]([Cl:55])=[CH:49][C:47]=2[N:48]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C(Cl)Cl.CC#N.CCOC(C)=O>[CH2:14]([O:13][C@@H:12]1[C@H:21]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:30]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:31][C@H:11]1[N:48]1[C:47]2[CH:49]=[C:50]([Cl:55])[C:51]([Cl:54])=[C:52]([Cl:53])[C:46]=2[N:45]=[C:44]1[Cl:43])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 156026611-O-p-nitrobenzoyl-2,3,5-tri-O-benzyl-beta-D-ribofuranoseHCID 178478312HCID 178478312, compound

Product 1

HCID 228765561-(2,3,5-Tri-O-benzyl-beta-D-ribofuranosyl)-2,4,5,6-tetrachlorobenzimidazoleYield 45%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

For the preparation of 1-O-chloro-2,3,5-tri-O-benzyl-D-ribofuranose, HCl gas was allowed to pass through a solution of 1-O-p-nitrobenzoyl-2,3,5-tri-O-benzyl-β-D-ribofuranose (1.479 g, 2.6 mmol) in 10 mL of dry CH2Cl2 at 0° C. for 15 min. The resulting suspension was quickly filtered and the filtrate was evaporated. The residue was coevaporated with dry MeCN and then dissolved in 5 mL of dry MeCN for immediate use in the subsequent glycosylation reaction. To a mixture of 13 (0.512 g, 2 mmol) in 10 mL of dry MeCN, was added 0.5 mL (2 mmol) of BSA. The reaction mixture was stirred at 75° C. for 20 min. This solution was treated with the above MeCN solution of the blocked carbohydrate and 0.464 mL (2.4 mmol) of TMSOTf at 70° C. for 20 min. The reaction mixture was cooled and diluted with EtOAc (50 mL). The EtOAc solution was washed with sat. NaHCO3 solution (50 mL×2), sat. NaCl solution (50 mL), dried (Na2SO4), and evaporated. The residue was chromatographed on a silica column (1.9×38 cm, eluted with hexane, 10%, 15% EtOAc/hexane). Evaporation of fractions 30-37 (15 mL per fraction) gave 0.593 g (45%) of 91a as a colorless syrup. MS: (El) m/e 658.0780 (2%, M+ =658.0774), 1H NMR (DMSO-d6): d 7.93 (s, 1, 7-H), 7.35, 6.92 (2×m, 15, 3×PhCH2), 5.99 (d, 1, 1'-H, J1'-2' =8.0 Hz), 4.72, 4.58, 4.35 (3×m, 9, 2'-H, 3'-H, and 3×PhCH2), 3.76 (dd, 1, 5'-H, J4'-5' =2.0 Hz, J5'-5" =11.0 Hz), 3.65 (dd, 1, 5"-H, J4'-5" =2.5 Hz), 13C NMR (DMSO-d6): d 142.00 (C2), 138.40 (C3a), 137.81. 137.44, 136.74 (3×PhCH2), 131.34 (C7a), 128.08, 128.03. 127.59, 127.40, 127.32, 127.28, 126.97 (3×PhCH2 and C4), 124.64, 122,52 (C5 and C6), 112.65 (C7), 87.46 (C1'), 83.03, 77.08, 74.92 (C2', C3', and C4'), 72.43, 71.44, 71.28 (3×PhCH2), 69.22 (C5'),

Workup

  1. filtrationThe resulting suspension was quickly filtered
  2. customthe filtrate was evaporated
  3. dissolutiondissolved in 5 mL of dry MeCN for immediate use in the subsequent glycosylation reaction
  4. additionwas added 0.5 mL (2 mmol) of BSA
  5. temperatureThe reaction mixture was cooled
  6. washThe EtOAc solution was washed with sat. NaHCO3 solution (50 mL×2), sat. NaCl solution (50 mL)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customThe residue was chromatographed on a silica column (1.9×38 cm, eluted with hexane, 10%, 15% EtOAc/hexane)
  10. customEvaporation of fractions 30-37 (15 mL per fraction)

Sources & evidence

ORD record
ord-a7e8671cb2ef46baa07260bd9886f707
Source dataset
uspto-grants-1998_01
Patent number
US05712255

Reaction notes

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