Methanol → (S)-2-{(R)-4-[4-(2-hydroxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide

HRID 1433778Notes

Reaction equation

HRID 1433778 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:38])[C@@H:11]([N:17]1[C:21](=[O:22])[C@@H:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][O:32]C(C)(C)C)=[CH:25][CH:24]=2)[NH:19][C:18]1=[O:37])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14].C[Si](I)(C)C.CO>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:38])[C@@H:11]([N:17]1[C:21](=[O:22])[C@@H:20]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH2:30][CH2:31][OH:32])=[CH:27][CH:28]=2)[NH:19][C:18]1=[O:37])[CH2:12][C:13]([CH3:16])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 887MethanolHCID 85247Trimethylsilyl iodideHCID 69303691(S)-2-{(R)-4-[4-(2-tert-butoxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide

Product 1

HCID 57935183(S)-2-{(R)-4-[4-(2-hydroxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amideYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-2-{(R)-4-[4-(2-tert-butoxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide (295 mg, 0.46 mmol) in dichloromethane (3 mL) at 0° C. under an atmosphere of dry argon was slowly added a solution of trimethylsilyl iodide (183 uL, 1.3 mmol) in dichloromethane (1 mL). The reaction mixture stirred at ambient temperature for 2 hours. Methanol (0.5 mL) was added to quench the reaction. The reaction mixture extracted with dichloromethane and the organic layer was washed sequentially with saturated aqueous sodium carbonate, 5% aqueous sodium thiosulfate, brine, then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel gradient eluted from 100% hexane up to 50% ethyl acetate/50% hexane over 30 minutes. Concentration of the product containing fractions gave (S)-2-{(R)-4-[4-(2-hydroxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide as a white solid (126 mg, 47%).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe reaction mixture extracted with dichloromethane
  4. washthe organic layer was washed sequentially with saturated aqueous sodium carbonate, 5% aqueous sodium thiosulfate, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography over silica gel gradient
  9. washeluted from 100% hexane up to 50% ethyl acetate/50% hexane over 30 minutes
  10. additionConcentration of the product containing fractions

Sources & evidence

ORD record
ord-8789484f07c0403d838fbeb55c326a86
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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