Potassium Carbonate → (R,Z)-3-(2-{4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-(prop-1-en-1-yl)phenyl]-3-methylpiperazin-1-yl}-2-oxoethyl)-5-[4-(1-methylethoxy)phenyl]-5-methylimidazolidine-2,4-dione

HRID 1038556Notes

Reaction equation

HRID 1038556 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][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38]([C:41]([O:50]COC)([C:46]([F:49])([F:48])[F:47])[C:42]([F:45])([F:44])[F:43])=[CH:37][C:36]=2/[CH:54]=[CH:55]\[CH3:56])[C@H:31]([CH3:57])[CH2:30]1)=[O:28].Cl.C(OCC)(=O)C>CN(C)C=O.C(OCC)(=O)C.O>[F:48][C:46]([F:47])([F:49])[C:41]([C:38]1[CH:39]=[CH:40][C:35]([N:32]2[CH2:33][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])[CH2:30][CH:31]2[CH3:57])=[C:36](/[CH:54]=[CH:55]\[CH3:56])[CH:37]=1)([OH:50])[C:42]([F:45])([F:44])[F:43]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 30521535-methyl-5-[4-(propan-2-yloxy)phenyl]imidazolidine-2,4-dioneHCID 21866389Hydrogen chloride-ethyl acetateHCID 86647202HCID 86647202, compound

Product 1

HCID 86647201(R,Z)-3-(2-{4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-(prop-1-en-1-yl)phenyl]-3-methylpiperazin-1-yl}-2-oxoethyl)-5-[4-(1-methylethoxy)phenyl]-5-methylimidazolidine-2,4-dioneYield 83.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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, (R,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}-3-methylpiperazin-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 crude product was dissolved in ethyl acetate (1.0 mL), added a solution of 4N-hydrochloric acid-ethyl acetate (1.0 mg), and 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 (R,Z)-3-(2-{4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-(prop-1-en-1-yl)phenyl]-3-methylpiperazin-1-yl}-2-oxoethyl)-5-[4-(1-methylethoxy)phenyl]-5-methylimidazolidine-2,4-dione (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. customThe obtained crude product
  7. stirringstirred at room temperature for 1 hour
  8. extractiona saturated aqueous solution of sodium hydrogen carbonate, and extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b796d39c66c3454a9720b1ab1a7c6506
Source dataset
uspto-grants-2013_10
Patent number
US08551985B2

Reaction notes

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