Sodium Iodide → HCID 67261265, compound

HRID 2368790Notes

Reaction equation

HRID 2368790 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([C:11]1[CH:12]=[N:13][C:14]([O:17]C)=[CH:15][CH:16]=1)O.[I-].[Na+].C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.C[Si](Cl)(C)C.[O-]S([O-])=O.[Na+].[Na+]>C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:11]1[CH:16]=[CH:15][C:14](=[O:17])[NH:13][CH:12]=1

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 24437Sodium SulfiteHCID 67257315HCID 67257315, compound

Product 1

HCID 67261265HCID 67261265, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (2,4-difluoro-phenyl)-(6-methoxy-pyridin-3-yl)methanol 2 (2.28 g, 9.1 mmol), sodium iodide (5.45 g, 36.4 mmol), triethylsilane (2.2 ml, 13.6 mmol) in anhydrous acetonitrile (21 ml) and was stirred at room temperature. TFA (1.1 ml, 14.3 mmol) was added at a rate that maintained the temperature below 30° C.; TMSCl (5.8 ml, 45.5 mmol) was added, and the batch was heated at 70° C. for 3 h. Upon cooling to 55° C., a 0.8 M Na2SO3 (11.4 ml) was added, and the reaction mixture was concentrated in vacuo to 20 ml. A solution of 0.15 M Na2SO3 (11.4 ml) was added, the mixture was stirred at room temperature overnight. A solution of 1.4 M K2CO3 (13.6 ml) was added and cooled to 0° C. The crude product was extracted with ethyl acetate (60 ml) and washed with 0.15 M Na2SO3 (20 ml) and water (60 ml) and dried over anhydrous sodium sulfate. The mixture was distilled, and the residue was purified by flash column chromatography on silica gel (chloroform:methanol, 90:10). Yield 1.89 g (94%). 1H NMR (CDCl3, 500 MHz): δ 13.35 (s, 1H), 7.36-6.79 (m, 7H), 6.53 (d, 1H, J=9.2 Hz), 3.71 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 164.7, 162.4, 160.4, 143.2, 132.7, 131.2, 122.3, 120.3, 118.4, 111.4, 104.1, 30.3.

Workup

  1. temperaturemaintained the temperature below 30° C.
  2. temperaturethe batch was heated at 70° C. for 3 h
  3. temperatureUpon cooling to 55° C.
  4. concentrationthe reaction mixture was concentrated in vacuo to 20 ml
  5. additionA solution of 0.15 M Na2SO3 (11.4 ml) was added
  6. stirringthe mixture was stirred at room temperature overnight
  7. additionA solution of 1.4 M K2CO3 (13.6 ml) was added
  8. temperaturecooled to 0° C
  9. extractionThe crude product was extracted with ethyl acetate (60 ml)
  10. washwashed with 0.15 M Na2SO3 (20 ml) and water (60 ml)
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe mixture was distilled
  13. customthe residue was purified by flash column chromatography on silica gel (chloroform:methanol, 90:10)

Sources & evidence

ORD record
ord-0b81e01675cd482eb8c0de04b93ec2b0
Source dataset
uspto-grants-2014_04
Patent number
US08703801B2

Reaction notes

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