Lithium Hexamethyldisilazide → 1-Cyclopropanesulfonyl-4,5,7-trifluoro-3-(2-fluoro-4-iodo-phenyl)-1,3-dihydro-benzimidazol-2-one

HRID 424005Notes

Reaction equation

HRID 424005 reaction equation
[F:1][C:2]1[C:10]2[NH:9][C:8](=[O:11])[N:7]([C:12]3[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=3[F:19])[C:6]=2[C:5]([F:20])=[C:4]([F:21])[CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:32]1([S:35](Cl)(=[O:37])=[O:36])[CH2:34][CH2:33]1>C1COCC1>[CH:32]1([S:35]([N:9]2[C:10]3[C:2]([F:1])=[CH:3][C:4]([F:21])=[C:5]([F:20])[C:6]=3[N:7]([C:12]3[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=3[F:19])[C:8]2=[O:11])(=[O:37])=[O:36])[CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 2760919Cyclopropanesulfonyl chlorideHCID 593863794,6,7-Trifluoro-1-(2-Fluoro-4-iodo-phenyl)-1,3-dihydrobenzoimidazole-2-one

Product 1

HCID 666743751-Cyclopropanesulfonyl-4,5,7-trifluoro-3-(2-fluoro-4-iodo-phenyl)-1,3-dihydro-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 4,6,7-trifluoro-1-(2-fluoro-4-iodo-phenyl)-1,3,-dihydrobenzimidazol-2-one (0.2 gm, 0.41 mmol) in dry THF (4 ml) under nitrogen was cooled to −78° C. and a solution of 1.0 M LiHMDS (0.41 ml, 0.41 mmol) was added slowly. (2 ml) followed by addition of cyclopropanesulfonyl chloride (0.050 ml, 0.49 mmol). This reaction mixture was kept stirring at room temperature for 16 hours, concentrated to dryness and was taken into EtOAc. The EtOAc was washed with water, dried over sodium sulfate and concentrated to dryness. The residue obtained 1-cyclopropanesulfonyl-4,5,7-trifluoro-3-(2-fluoro-4-iodo-phenyl)-1,3-dihydro-benzimidazol-2-one 5 was taken into dioxane (2 ml) and to this 1.0 N NaOH (0.5 ml) was added and kept stirring at room 50° C. for 16 hours. TLC indicated incomplete reaction, the product was purified by HPLC to provide off-white solid (4.4 mg) M+H+: 484.7, M−H+: 486.7. 1H NMR (CDCl3, 300 MHZ): 0.9-1.1-(m, 2H); 1.1-1.2 (m, 2H); 2.45-2.55 (m, 1H); 6.05 (s, 1H); 6.44-6.54 (m, 1H); 7.1 (s, 1H); 7.4-7.7 (d, 1H); 7.38-7.44 (dd, 1H); m/z=485 [M−1]−.

Workup

  1. concentrationconcentrated to dryness
  2. washThe EtOAc was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-e4fd941580694620b0f3d79a3fb651df
Source dataset
uspto-grants-2012_01
Patent number
US08101799B2

Reaction notes

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