Sodium Iodide → HCID 10152326, compound

HRID 1297781Notes

Reaction equation

HRID 1297781 reaction equation
C([Si](C)(C)[O:6][C:7]1[C:12]([CH3:13])=[CH:11][C:10]([C:14]2([C:24]3[CH:29]=[C:28]([CH3:30])[C:27]([O:31][Si](C(C)(C)C)(C)C)=[C:26]([CH3:39])[CH:25]=3)[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][C:15]2=[O:23])=[CH:9][C:8]=1[CH3:40])(C)(C)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:53][C:54]1[CH:61]=[C:60]([F:62])[CH:59]=[CH:58][C:55]=1[CH2:56]Br.[I-].[Na+]>O1CCCC1.CO>[F:53][C:54]1[CH:61]=[C:60]([F:62])[CH:59]=[CH:58][C:55]=1[CH2:56][N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]([C:10]2[CH:11]=[C:12]([CH3:13])[C:7]([OH:6])=[C:8]([CH3:40])[CH:9]=2)([C:24]2[CH:25]=[C:26]([CH3:39])[C:27]([OH:31])=[C:28]([CH3:30])[CH:29]=2)[C:15]1=[O:23]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 2733832Lithium HexamethyldisilazideHCID 58914719HCID 58914719, compound2×

Product 1

HCID 10152326HCID 10152326, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Combine a solution of 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1,3-dihydro-indol-2-one (0.15 g, 0.250 mmol) in anhydrous tetrahydrofuran (6 ml), with 0.750 mL of 1N lithium bis(trimethlysilyl)amide in tetrahydrofuran. Stir the resulting mixture at room temperature for 0.25 h. In a separate flask, prepare a solution of 2,4-difluorobenzyl bromide (0.155 g, 0.750 mmol) and sodium iodide (0.011 g, 0.075 mmol) in anhydrous tetrahydrofuran. Stir at room temperature for 0.25 h then add this solution to the 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1,3-dihydro-indol-2-one. Stir and heat the resulting mixture at 60° C. for 18 h. Cool to ambient temperature and dilute with 6 ml of methanol. Absorb the crude intermediate on 1 g of silica gel and evaporate the solvent under reduced pressure. Chromatograph this residue on a silica gel column eluting with 1:9 ethyl acetate/hexane. Combine the isolated intermediate, 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1-(2,4-difluoro-benzyl)-1,3-dihydro-indol-2-one, with 4 ml of 1N CsF in methanol. Stir and heat at 60 C for 1 h then remove solvent in vacuuo. Dissolve the residue in 10 ml of water and extract with ethyl acetate (4×7 ml). Pass the ethyl acetate solution over anhydrous sodium sulfate and concentrate under vacuum. Triturate the residue with diethyl ether to obtain 0.097 g (78%) of the titled compound as granular crystals: LCMS (system 2) tR=4.13 min (100%), ESMS (M+1) m/z=499.56

Workup

  1. stirringStir at room temperature for 0.25 h
  2. stirringStir
  3. temperatureheat the resulting mixture at 60° C. for 18 h
  4. temperatureCool to ambient temperature
  5. customAbsorb the crude intermediate on 1 g of silica gel
  6. customevaporate the solvent under reduced pressure
  7. washChromatograph this residue on a silica gel column eluting with 1:9 ethyl acetate/hexane
  8. stirringStir
  9. temperatureheat at 60 C for 1 h
  10. dissolutionDissolve the residue in 10 ml of water
  11. extractionextract with ethyl acetate (4×7 ml)
  12. concentrationPass the ethyl acetate solution over anhydrous sodium sulfate and concentrate under vacuum
  13. customTriturate the residue with diethyl ether

Sources & evidence

ORD record
ord-76f82a428f544e0f93e787d24d14548c
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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