Iodine → 2',3'-Dideoxy-5-iodocytidine

HRID 1029374

Reaction equation

HRID 1029374 reaction equation
[C@@H:1]1([N:8]2[CH:15]=[CH:14][C:12]([NH2:13])=[N:11][C:9]2=[O:10])[O:7][C@H:4]([CH2:5][OH:6])[CH2:3][CH2:2]1.[I:16]I>CO.ClCCl>[I:16][C:14]1[C:12]([NH2:13])=[N:11][C:9](=[O:10])[N:8]([CH:15]=1)[C@@H:1]1[O:7][C@H:4]([CH2:5][OH:6])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 807IodineHCID 24066Dideoxycytidine

Product 1

HCID 146301042',3'-Dideoxy-5-iodocytidineYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of 2',3'-dideoxycytidine (2.11 g, 10 mmol, Raylo) and mercuric acetate (3.35 g, 10.5 mmol, Fisher) in 50 mL of methanol was refluxed for 19 hours. The resulting white suspension was diluted with methanol (50 mL) and dichloromethane (100 mL). Iodine (3.05 g, 12 mmol) was added and the suspension was stirred at 25°. After 4 hours, the free base form of AG3 X4A resin (20 mL, 38 meq, Bio-Rad) was added and hydrogen sulfide was bubbled into the reaction for 15 minutes. Complete precipitation of mercury(II) was verified by TLC. The reaction was filtered through filter aid and the filter aid was washed with 1:1 methanol-dichloromethane. The filtrate was evaporated onto silica gel (10 g) and the loaded silica gel was placed on top of a 150 g silica gel column. Elution with 5%, 10% and 20% methanol in dichloromethane afforded 2.79 g (83%) of iodide 19 as a colorless crystalline solid. Two recrystallizations from boiling water afforded, after vacuum-drying at 50°, large, analytically-pure prisms (mp: d 178°).

Workup

  1. additionthe free base form of AG3 X4A resin (20 mL, 38 meq, Bio-Rad) was added
  2. customhydrogen sulfide was bubbled into the reaction for 15 minutes
  3. customComplete precipitation of mercury(II)
  4. filtrationThe reaction was filtered
  5. filtrationthrough filter aid
  6. washthe filter aid was washed with 1:1 methanol-dichloromethane
  7. customThe filtrate was evaporated onto silica gel (10 g)
  8. washElution with 5%, 10% and 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-58c25d147f4c4516a02128e4ae8f433d
Source dataset
uspto-grants-1992_04
Patent number
US05102785

Linked notes

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