Water → (2R,5S,Z)-3-(2-{4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-(prop-1-en-1-yl)phenyl]-2,5-dimethylpiperazin-1-yl}-2-oxoethyl)-5-(4-isopropoxyphenyl)-5-methylimidazolidine-2,4-dione

HRID 1038561Notes

Reaction equation

HRID 1038561 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2([CH3:18])[NH:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:7][CH:6]=1)[CH3:3].C(=O)([O-])[O-].[K+].[K+].Br[CH2:26][C:27]([N:29]1[CH2:34][C@H:33]([CH3:35])[N:32]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([O:51]COC)([C:47]([F:50])([F:49])[F:48])[C:43]([F:46])([F:45])[F:44])=[CH:38][C:37]=2/[CH:55]=[CH:56]\[CH3:57])[CH2:31][C@H:30]1[CH3:58])=[O:28].O>CN(C)C=O>[F:45][C:43]([F:44])([F:46])[C:42]([C:39]1[CH:40]=[CH:41][C:36]([N:32]2[CH:33]([CH3:35])[CH2:34][N:29]([C:27](=[O:28])[CH2:26][N:13]3[C:12](=[O:17])[C@@:11]([C:8]4[CH:7]=[CH:6][C:5]([O:4][CH:2]([CH3:1])[CH3:3])=[CH:10][CH:9]=4)([CH3:18])[NH:15][C:14]3=[O:16])[C@H:30]([CH3:58])[CH2:31]2)=[C:37](/[CH:55]=[CH:56]\[CH3:57])[CH:38]=1)([OH:51])[C:47]([F:50])([F:49])[F:48]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 30521535-methyl-5-[4-(propan-2-yloxy)phenyl]imidazolidine-2,4-dioneHCID 86647204(2R,5S,Z)-2-bromo-1-(4-{4-[1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl]-2-(prop-1-en-1-yl)phenyl}-2,5-dimethylpiperazin-1-yl)ethanone

Product 1

HCID 86647203(2R,5S,Z)-3-(2-{4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-(prop-1-en-1-yl)phenyl]-2,5-dimethylpiperazin-1-yl}-2-oxoethyl)-5-(4-isopropoxyphenyl)-5-methylimidazolidine-2,4-dioneYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-[4-(1-Methylethoxy)phenyl]-5-methylimidazolidine-2,4-dione (7.7 mg, 0.0311 mmol) was dissolved in N,N-dimethylformamide (500 μL), added potassium carbonate (8.6 mg, 0.0622 mmol) under ice-cold conditions, and the mixture was stirred at room temperature for 5 minutes. Then, under ice-cold conditions, (2R,5S,Z)-2-bromo-1-(4-{4-[1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl]-2-(prop-1-en-1-yl)phenyl}-2,5-dimethylpiperazin-1-yl)ethanone (17 mg, 0.0311 mmol) was added and stirred at room temperature for 18 hours. Under ice-cold conditions, the reaction solution was added water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residue was dissolved in ethyl acetate (1.0 mL), added a solution of 4N-hydrochloric acid-ethyl acetate (1.0 mg), and the mixture was stirred at room temperature for 1 hour. Under ice-cold conditions, the reaction solution was added water and a saturated aqueous solution of sodium hydrogen carbonate, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (17.4 mg (yield 83%)) was obtained as a yellow oil.

Workup

  1. stirringstirred at room temperature for 18 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThe obtained residue was dissolved in ethyl acetate (1.0 mL)
  7. additionadded a solution of 4N-hydrochloric acid-ethyl acetate (1.0 mg)
  8. stirringthe mixture was stirred at room temperature for 1 hour
  9. additionUnder ice-cold conditions, the reaction solution was added water
  10. extractiona saturated aqueous solution of sodium hydrogen carbonate, and extracted with ethyl acetate
  11. washThe organic layer was washed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c4014e49cfc94f2b8d6ce58110303ff4
Source dataset
uspto-grants-2013_10
Patent number
US08551985B2

Reaction notes

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