Iodine → Acetic acid (2R,3R,4R,5R)-3,4-diacetoxy-5-(6-chloro-2-iodo-purin-9-YL)-tetrahydro-furan-2-ylmethyl ester

HRID 16053

Reaction equation

HRID 16053 reaction equation
N(OCCC(C)C)=O.[C:9]([O:12][CH2:13][C@@H:14]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@@H:17]([O:23][C:24](=[O:26])[CH3:25])[C@H:16]([N:27]2[CH:35]=[N:34][C:33]3[C:28]2=[N:29][C:30](N)=[N:31][C:32]=3[Cl:36])[O:15]1)(=[O:11])[CH3:10].II.C(I)[I:41].[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1.[Cu]I>[C:9]([O:12][CH2:13][C@@H:14]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@@H:17]([O:23][C:24](=[O:26])[CH3:25])[C@H:16]([N:27]2[CH:35]=[N:34][C:33]3[C:28]2=[N:29][C:30]([I:41])=[N:31][C:32]=3[Cl:36])[O:15]1)(=[O:11])[CH3:10]

Participants

8

Reactant 5

HCID 807IodineHCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 24477Sodium ThiosulfateHCID 10788628(2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate

Product 1

HCID 482588Acetic acid (2R,3R,4R,5R)-3,4-diacetoxy-5-(6-chloro-2-iodo-purin-9-YL)-tetrahydro-furan-2-ylmethyl ester

Reagents, catalysts & solvents 2

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

Procedure

Isoamyl nitrite (5 mL, 37 mmol) was added to a mixture of 5.12 g (12 mmol) [(2R,3R,4R,5R)-3-,4-diacetyloxy-5-(2-amino-6-chloropurin-9-yl)oxolan-2-yl]methy 1 acetate (6.3), I2 (3.04 g, 12 mmol), CH2I2 (10 mL, 124 mmol), and CuI (2.4 g, 12.6 mmol) in THF (60 mL). The mixture was heated under reflux for 45 minutes and then allowed to cool to room temperature. To this solution was added 100 ml of saturated Na2S2O3. This step removed the reddish color. The aqueous layer was extracted 3× with chloroform, which was pooled, dried over MgSO4, and concentrated under reduced pressure. The product was then purified over a silica gel column using CHCl3-MeOH (98:2) to collect [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-chloro-2-iodopurin-9-yl)oxolan-2-yl]methyl acetate (6.4) (80% crystallized from EtOH). 1H NMR (300 MHz, CDCl3) 8.20 (s, 1H H-8), 6.17 (d, J=5.41 Hz, 1H, H-1), 5.75 (t, J=5.39 Hz, 1H, H-2), 5.56 (t, J=5.40 Hz, 1H, 1H-3), 4.38 (m, 3H, 1H-4,5), 2.14 (s, 1H, Ac), 2.11 (s, 1H, Ac), 2.10 (s, 1H, Ac).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 45 minutes
  3. customThis step removed the reddish color
  4. extractionThe aqueous layer was extracted 3× with chloroform, which
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe product was then purified over a silica gel column
  8. customto collect [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-chloro-2-iodopurin-9-yl)oxolan-2-yl]methyl acetate (6.4) (80% crystallized from EtOH)

Sources & evidence

ORD record
ord-010ac816cca847b6816acb77f5c7b247
Source dataset
uspto-grants-2010_06
Patent number
US07737127B2

Linked notes

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