Sodium Iodide → 2-(5-chloro-2-fluorophenyl)-4-iodo-5-methyl-6,7-dihydro-5H-cyclopentapyrimidine

HRID 1010868Notes

Reaction equation

HRID 1010868 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[N:13]=[C:12](O)[C:11]3[CH:15]([CH3:18])[CH2:16][CH2:17][C:10]=3[N:9]=2)[CH:7]=1.[Na+].[I-:21]>O=P(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[N:13]=[C:12]([I:21])[C:11]3[CH:15]([CH3:18])[CH2:16][CH2:17][C:10]=3[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 178423154HCID 178423154, compound

Product 1

HCID 211043082-(5-chloro-2-fluorophenyl)-4-iodo-5-methyl-6,7-dihydro-5H-cyclopentapyrimidine

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A suspension of 2-(5-chloro-2-fluorophenyl)-5-methyl-6,7-dihydro-5H-cyclopentapyrimidin-4-ol (200 mg, 0.72 mmol, 1 eq) in POCl3 (5 ml) was stirred under reflux for 1 h. The solution was then cooled to room temperature and concentrated under reduced pressure to give a white solid. The residual POCl3 was removed by azeotrope with chloroform. To a suspension of the crude iminochloride in a 57% HI solution in water (5 ml) at r.t. was added NaI (540 mg, 3.60 mmol, 5 eq). The reaction mixture was stirred at r.t. overnight and then poured onto ice. The product was extracted with chloroform and the aqueous layer was neutralized with NaHCO3 and extracted further with chloroform. The organic layers were combined washed with brine, dried (MgSO4), filtered and evaporated in vacuo to provide a crude residue 2-(5-chloro-2-fluorophenyl)-4-iodo-5-methyl-6,7-dihydro-5H-cyclopentapyrimidine which was not further purified.

Workup

  1. temperatureunder reflux for 1 h
  2. concentrationconcentrated under reduced pressure
  3. customto give a white solid
  4. customThe residual POCl3 was removed by azeotrope with chloroform
  5. additionTo a suspension of the crude iminochloride in a 57% HI solution in water (5 ml) at r.t.
  6. stirringThe reaction mixture was stirred at r.t. overnight
  7. additionpoured onto ice
  8. extractionThe product was extracted with chloroform
  9. extractionextracted further with chloroform
  10. washThe organic layers were combined washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-f320bb843ef14ad2b25cb0efb0156a99
Source dataset
uspto-grants-2011_07
Patent number
US07977342B2

Reaction notes

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