Methyl morpholine oxide → 4-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-hydroxymethyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

HRID 1245539Notes

Reaction equation

HRID 1245539 reaction equation
[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[Cl:37])[C@@H:14]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[C@@:12]3([CH:38]=C)[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1.C[N+]1([O-])CC[O:44]CC1.[BH4-].[Na+]>O1CCOCC1.CCOC(C)=O.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[Cl:37])[C@@H:14]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[C@@:12]3([CH2:38][OH:44])[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 4311764Sodium borohydrideHCID 872853624-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-vinyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 872853644-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-hydroxymethyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidineYield 52.1%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of the compound from Example 137, Step B (300 mg, 0.48 mmol) in 1,4-dioxane (5 mL) were added N-methylmorpholine-N-oxide (300 mg, 2.56 mmol) and osmium tetroxide (4% solution in water, 0.3 mL). The mixture was stirred in the dark for 14 h. The precipitate was removed by filtration through a celite plug, diluted with water (3×), and extracted with EtOAc. The EtOAc layer was dried over Na2SO4 and concentrated in vacuo. The oily residue was taken up in dichloromethane (5 mL) and stirred over NaIO4 on silica gel (3 g, 10% NaIO4) for 12 h. The silica gel was removed by filtration and the residue was evaporated and taken up in absolute ethanol (5 mL). The solution was cooled in an ice bath and sodium borohydride (300 mg, 8 mmol) was added in small portions. The resulting mixture was stirred at room temperature for 4 h and then diluted with EtOAc. The organic layer was washed with water (2×20 mL), brine (20 mL) and dried over Na2SO4. The solvent was evaporated and the residue purified by flash chromatography (SiO2, 2:1 hexanes/EtOAc) to give the title compound (160 mg, 0.25 mmol) as white flakes.

Workup

  1. customThe precipitate was removed by filtration through a celite plug
  2. additiondiluted with water (3×)
  3. extractionextracted with EtOAc
  4. dry with materialThe EtOAc layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. stirringstirred over NaIO4 on silica gel (3 g, 10% NaIO4) for 12 h
  7. customThe silica gel was removed by filtration
  8. customthe residue was evaporated
  9. temperatureThe solution was cooled in an ice bath
  10. stirringThe resulting mixture was stirred at room temperature for 4 h
  11. washThe organic layer was washed with water (2×20 mL), brine (20 mL)
  12. dry with materialdried over Na2SO4
  13. customThe solvent was evaporated
  14. customthe residue purified by flash chromatography (SiO2, 2:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-36f5a6bc94a94373be46db515f7d93ad
Source dataset
uspto-grants-2006_10
Patent number
US07125855B2

Reaction notes

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