Sodium hydride → (R)-1-(5-acetoxyhexyl)-7-benzyl-3,8-dimethylxanthine

HRID 1814920Notes

Reaction equation

HRID 1814920 reaction equation
[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][C:13](=[O:18])[N:12]([CH3:19])[C:11]=2[N:10]=[C:9]1[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:23]([O:26][CH:27]([CH3:33])[CH2:28][CH2:29][CH2:30][CH2:31][Cl:32])(=[O:25])[CH3:24]>CS(C)=O>[C:23]([O:26][CH:27]([CH3:33])[CH2:28][CH2:29][CH2:30][CH2:31][Cl:32])(=[O:25])[CH3:24].[C:23]([O:26][C@H:27]([CH3:33])[CH2:28][CH2:29][CH2:30][CH2:31][N:14]1[C:15](=[O:17])[C:16]2[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:9]([CH3:20])=[N:10][C:11]=2[N:12]([CH3:19])[C:13]1=[O:18])(=[O:25])[CH3:24]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 36180515-Acetoxy-1-chlorohexaneHCID 147126087-Benzyl-3,8-dimethylxanthine

Product 2

HCID 36180515-Acetoxy-1-chlorohexaneHCID 54438002(R)-1-(5-acetoxyhexyl)-7-benzyl-3,8-dimethylxanthineYield 154.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

7-Benzyl-3,8-dimethylxanthine (500 mg, 1.85 mmol) was added to a suspension of sodium hydride (50.5 mg) in anhydrous dimethylsulfoxide (20 ml). After stirring for 30 minutes, (R) 5-acetoxy-1-chlorohexane (357 mg) was added and the mixture was warmed to 70-80° C. for 12 hours. The (R) 5-acetoxy-1-chlorohexane was prepared according to methods described in U.S. Pat. No. 5,629,423 issued to Klein, J. P., Leigh, A. J., Michnick, J., Kumar, A. M., Underiner, G. E., on May 13, 1997. After cooling to room temperature, the reaction wash quenched by the addition of water (50 ml) and extracted with ethyl acetate (3×75 ml). The combined extracts were washed with water (2×50 ml), washed with saturated aqueous sodium chloride solution (50 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate to give (R)-1-(5-acetoxyhexyl)-7-benzyl-3,8-dimethylxanthine (638 mg).

Workup

  1. temperatureAfter cooling to room temperature
  2. washthe reaction wash
  3. customquenched by the addition of water (50 ml)
  4. extractionextracted with ethyl acetate (3×75 ml)
  5. washThe combined extracts were washed with water (2×50 ml)
  6. washwashed with saturated aqueous sodium chloride solution (50 ml)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-2b4412f1222849f29f3b211935407cc9
Source dataset
uspto-grants-2005_04
Patent number
US06878715B1

Reaction notes

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