Sodium Iodide → 2-Iodo-4-[5-(4-morpholinylcarbonyl)-2-pyridinyl]phenol

HRID 494796Notes

Reaction equation

HRID 494796 reaction equation
[N:1]1([C:7]([C:9]2[CH2:14][NH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[I-:22].[Na+].[OH-].[Na+].Cl[O-].[Na+]>CO>[I:22][C:17]1[CH:16]=[C:15]([C:12]2[CH:11]=[CH:10][C:9]([C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:8])=[CH:14][N:13]=2)[CH:20]=[CH:19][C:18]=1[OH:21]

Participants

6

Reactant 4

HCID 5238Sodium Iodide2×HCID 14798Sodium HydroxideHCID 222746924-[5-(4-Morpholinylcarbonyl)-1,6-dihydro-2-pyridinyl]phenolHCID 23665760Sodium Hypochlorite

Product 1

HCID 1357210712-Iodo-4-[5-(4-morpholinylcarbonyl)-2-pyridinyl]phenolYield 61.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of Example 44B (4.25 g, 15.0 mmol) sodium iodide (2.36 g, 15.7 mmol) and sodium hydroxide (0.63 g, 15.7 mmol) was stirred in methanol (90 mL) with heating until a clear solution was obtained. The solution was then cooled to 0° C. and to this was slowly added sodium hypochlorite (22 mL of 5.25%, 1.15 g, 15.5 mmol) (Clorox™) over 45 minutes. While maintaining 0° C., two sequential additions of NaI (0.3 g, 1.5 mmol) and Clorox (2.2 mL, 0.12 g, 1.5 mmol) were made both 2 hours and 4 hours later. The mixture was stirred for 12 hours at ambient temperature, quenched by the sequential addition of aqueous sodium thiosulfate (10 mL), water (800 mL) and sufficient aqueous sodium dihydrogen phosphate (NaH2PO4) to adjust the pH to 7. The mixture was extracted with dichloromethane, and the combined extracts dried (Na2SO4), filtered and concentrated under reduced pressure to give a tan foam. The product was crystallized from ethanol to give the titled compounds as a tan solid (3.78 g, 61%). MS (DCI) m/z 411 (M+H)+;

Workup

  1. temperaturewith heating until a clear solution
  2. customwas obtained
  3. customover 45 minutes
  4. temperatureWhile maintaining 0° C.
  5. customquenched by the sequential addition of aqueous sodium thiosulfate (10 mL), water (800 mL) and sufficient aqueous sodium dihydrogen phosphate (NaH2PO4)
  6. extractionThe mixture was extracted with dichloromethane
  7. dry with materialthe combined extracts dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a tan foam
  11. customThe product was crystallized from ethanol

Sources & evidence

ORD record
ord-28b0635d53984bd6bda851eb68143f4e
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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