Sodium borohydride → HCID 54132005, compound

HRID 1663525Notes

Reaction equation

HRID 1663525 reaction equation
[CH2:1]([O:8][C@:9]1([CH:33]=C)[C@@H:13]([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:23]2[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]2=[O:25])[C@H:10]1[OH:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I([O-])(=O)(=O)=[O:36].[Na+].[BH4-].[Na+]>C1COCC1.O.[Os](=O)(=O)(=O)=O.C(O)(C)(C)C>[CH2:1]([O:8][C@:9]1([CH2:33][OH:36])[C@@H:13]([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:23]2[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]2=[O:25])[C@H:10]1[OH:32])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 4311764Sodium borohydrideHCID 23667635Sodium periodateHCID 54435224HCID 54435224, compound

Product 1

HCID 54132005HCID 54132005, compoundYield 36.3%

Reagents, catalysts & solvents 4

HCID 6386tert-ButanolCatalystHCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of nucleoside 26 (2.00 g, 4.31 mmol) in a mixture of THF (15 cm3) and water (15 cm3) was added sodium periodate (2.76 g, 12.9 mmol) and a 2.5% solution of osmium tetraoxide in t-butanol (w/w, 0.54 cm3, 43 μmol). The reaction was stirred at room temperature for 18 h, quenched with water (50 cm3), and the mixture was extracted with dichloromethane (2×100 cm3). The combined extract was washed with saturated aqueous sodium hydrogen carbonate (3×75 cm3), dried (Na2SO4) and evaporated under reduced pressure. The residue was redissolved in a mixture of THF (15 cm3) and water (15 cm3), and sodium borohydride (488 mg, 12.9 mmol) was added. The reaction mixture was stirred at room temperature for 1 h, water (50 cm3) was added, and the mixture was extracted with dichloromethane (2×100 cm3). The combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×75 cm3) and dried (Na2SO4). The solvent was removed and the residue was purified by silica gel column chromatography using dichloromethane/methanol (98:2, v/v) as eluent to give nucleoside 27 as a white foam (732 mg, 36%). δH (CDCl3) 11.09 (1H, br s, NH), 7.41 (1H, d, J 1.0, 6-H), 7.38-7.26 (Bn), 6.16 (1H, d, J 2.6, 1′-H), 5.12 (1H, d, J 5.4, 2′-OH), 4.66-4.29 (6H, m, 2′-H, 4′-H, Bn), 4.02-3.96 (2H, m, 1″-Ha, 1″-Hb), 3.90 (1H, dd, J 7.2, 9.7, 5′-Ha), 3.79 (1H, dd, J 5.6, 9.7, 5′-Hb), 2.49 (1H, t, J 6.4, 1″-OH), 1.68 (3H, d, J 0.6, CH3); δC (CDCl3) 166.1 (C-4), 150.6 (C-2), 139.0, 137.9, 137.0 (C-6, Bn), 128.7, 128.6, 128.4, 128.3, 128.0 (Bn), 107.5 (C-5), 88.2 (C-1′), 88.1 (C-3′), 84.2 (C-4′), 73.7 (C-5′), 72.1 (C-2′), 69.3, 65.4 (Bn), 58.6 (C-1″), 12.3 (CH3).

Workup

  1. customquenched with water (50 cm3)
  2. extractionthe mixture was extracted with dichloromethane (2×100 cm3)
  3. extractionThe combined extract
  4. washwas washed with saturated aqueous sodium hydrogen carbonate (3×75 cm3)
  5. dry with materialdried (Na2SO4)
  6. customevaporated under reduced pressure
  7. additionwas added
  8. stirringThe reaction mixture was stirred at room temperature for 1 h
  9. extractionthe mixture was extracted with dichloromethane (2×100 cm3)
  10. washThe combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×75 cm3)
  11. dry with materialdried (Na2SO4)
  12. customThe solvent was removed
  13. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b8e411329f2248608f1c0c1f2957bd0c
Source dataset
uspto-grants-2011_10
Patent number
US08034909B2

Reaction notes

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