Iodine → (2R,3R,4S,5S)-4-(benzoyloxy)-2-(6-chloro-2-iodo-9H-purin-9-yl)-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate

HRID 1060554

Reaction equation

HRID 1060554 reaction equation
N(OCCCC)=O.[C:8]([O:16][C@@H:17]1[C@H:21]([O:22][C:23](=[O:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:20]([C:31]([NH:33][CH2:34][CH3:35])=[O:32])[O:19][C@H:18]1[N:36]1[CH:44]=[N:43][C:42]2[C:37]1=[N:38][C:39](N)=[N:40][C:41]=2[Cl:45])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.II.[I:49]CI>C1COCC1.[Cu]I>[C:8]([O:16][C@@H:17]1[C@H:21]([O:22][C:23](=[O:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:20]([C:31]([NH:33][CH2:34][CH3:35])=[O:32])[O:19][C@H:18]1[N:36]1[CH:44]=[N:43][C:42]2[C:37]1=[N:38][C:39]([I:49])=[N:40][C:41]=2[Cl:45])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 807IodineHCID 6346DiiodomethaneHCID 10996Butyl nitriteHCID 10143973(2R,3R,4S,5S)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzoyloxy)-5-[(ethylamino)carbonyl]-tetrahydro-3-furanyl benzoate

Product 1

HCID 10189909(2R,3R,4S,5S)-4-(benzoyloxy)-2-(6-chloro-2-iodo-9H-purin-9-yl)-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoateYield 78%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

n-Butyl nitrite (4.65 ml, 39.7 mmol) was added to a suspension of (2R,3R,4S,5S)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzoyloxy)-5-[(ethylamino)carbonyl]-tetrahydro-3-furanyl benzoate (Preparation 18) (8.10 g, 14.7 mmol), iodine (3.73 g, 14.7 mmol), copper(I) iodide (6.16 g, 32.3 mmol) and diiodomethane (12.55 ml, 155.8 mmol) in THF (100 ml) and the mixture was heated at reflux for 2.5 hours. The solution was allowed to cool to room temperature and the solvent was removed under reduced pressure. The residue was partitioned between aqueous sodium metabisulfite solution (5%, 100 ml) and dichloromethane (100 ml). The organic layer was separated, filtered through arbacel, dried (MgSO4) and solvent evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (99:1 by volume) to afford the title compound as a yellow foam (7.55 g, 78%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 2.5 hours
  3. customthe solvent was removed under reduced pressure
  4. customThe residue was partitioned between aqueous sodium metabisulfite solution (5%, 100 ml) and dichloromethane (100 ml)
  5. customThe organic layer was separated
  6. filtrationfiltered through arbacel
  7. dry with materialdried (MgSO4) and solvent
  8. customevaporated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (99:1 by volume)

Sources & evidence

ORD record
ord-2e8657f079d144818b82ea986a25658e
Source dataset
uspto-grants-2003_02
Patent number
US06525032B2

Linked notes

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