Isopropyl iodide → HCID 56932937, compound

HRID 1972638Notes

Reaction equation

HRID 1972638 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:39])[N:8]([CH2:9][C@H:10]2[CH2:15][N:14]([S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH2:13][CH2:12][N:11]2[C:24]2[CH:29]=[CH:28][C:27]([C:30]([OH:36])([CH3:35])[C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=2)[C:7](=[O:37])[NH:6][C:5]1=[O:38].I[CH:41]([CH3:43])[CH3:42]>CN(C=O)C>[CH3:3][C:4]1([CH3:39])[N:8]([CH2:9][C@H:10]2[CH2:15][N:14]([S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH2:13][CH2:12][N:11]2[C:24]2[CH:25]=[CH:26][C:27]([C:30]([OH:36])([CH3:35])[C:31]([F:32])([F:33])[F:34])=[CH:28][CH:29]=2)[C:7](=[O:37])[N:6]([CH:41]([CH3:43])[CH3:42])[C:5]1=[O:38]

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 66583199HCID 66583199, compound

Product 1

HCID 56932937HCID 56932937, compoundYield 21.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of sodium hydride (0.0203 g, 0.508 mmol, Sigma-Aldrich, St. Louis, Mo.) in DMF (1 mL) in a 5 mL vial, 5,5-dimethyl-1-(((2s)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-2,4-imidazolidinedione (0.090 g, 0.161 mmol, Example 228) in DMF (total 1.5 mL) was added dropwise at 0° C. The mixture was stirred at 0° C. for 15 min and 2-iodopropane (0.020 mL, 0.20 mmol, Sigma-Aldrich, St. Louis, Mo.) was added dropwise. The cold bath was removed and the mixture was stirred at room temperature for 12 h. The reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (20 mL). Saturated aqueous NaCl (20 mL) was added and the aqueous phase was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with saturated aqueous NaCl (80 mL). The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography (25 g of silica, 0 to 80% EtOAc in hexanes) to afford 5,5-dimethyl-3-(1-methylethyl)-1-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-2,4-imidazolidinedione (0.021 g) as a mixture of two isomers.

Workup

  1. customThe cold bath was removed
  2. stirringthe mixture was stirred at room temperature for 12 h
  3. customThe reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (20 mL)
  5. additionSaturated aqueous NaCl (20 mL) was added
  6. extractionthe aqueous phase was extracted with EtOAc (2×20 mL)
  7. washThe combined organic extracts were washed with saturated aqueous NaCl (80 mL)
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by silica gel chromatography (25 g of silica, 0 to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-81203ae29fea42b6903caa6c2b7cadee
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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