Phthalimide → 2-((1-(4-fluorophenyl)-2-((2,3,6-trifluoro benzyl)thio)-1H-imidazol-5-yl)methyl)isoindoline-1,3-dione

HRID 2368490Notes

Reaction equation

HRID 2368490 reaction equation
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:47][C:48]1[CH:53]=[CH:52][C:51]([N:54]2[C:58]([CH2:59]O)=[CH:57][N:56]=[C:55]2[S:61][CH2:62][C:63]2[C:68]([F:69])=[CH:67][CH:66]=[C:65]([F:70])[C:64]=2[F:71])=[CH:50][CH:49]=1>C1COCC1.C(OCC)(=O)C.O>[F:47][C:48]1[CH:53]=[CH:52][C:51]([N:54]2[C:58]([CH2:59][N:5]3[C:1](=[O:11])[C:2]4[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:4]3=[O:6])=[CH:57][N:56]=[C:55]2[S:61][CH2:62][C:63]2[C:68]([F:69])=[CH:67][CH:66]=[C:65]([F:70])[C:64]=2[F:71])=[CH:50][CH:49]=1

Participants

8

Reactant 4

HCID 6809Phthalimide2×HCID 11776Triphenylphosphine2×HCID 6034084Di-tert-butyl diazene-1,2-dicarboxylate2×HCID 71117330(1-(4-fluorophenyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazol-5-yl)methanol

Product 1

HCID 711177562-((1-(4-fluorophenyl)-2-((2,3,6-trifluoro benzyl)thio)-1H-imidazol-5-yl)methyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phthalimide (783 mg, 5.32 mmol), di-tert-butylazodicarboxylate (1.23 g, 5.32 mmol) and triphenyl phosphine (1.4 g, 5.32 mmol) were added to a solution of (1-(4-fluorophenyl)-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazol-5-yl)methanol (28) (980 mg, 2.66 mmol) in THF (30 mL) and the reaction was stirred overnight at room temperature. An additional equivalent of phthalimide, di-tert-butylazodicarboxylate and triphenyl phosphine was added and stirred overnight. Water and ethyl acetate were added and the layers were separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (0-100% EtOAc in hexanes) to afford 2-((1-(4-fluorophenyl)-2-((2,3,6-trifluoro benzyl)thio)-1H-imidazol-5-yl)methyl)isoindoline-1,3-dione (29) as an oil.

Workup

  1. stirringstirred overnight
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-58ff4a3eb3aa49809c8d9f5f2bb28ba3
Source dataset
uspto-grants-2014_04
Patent number
US08703776B2

Reaction notes

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