Sodium hydride → (R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthine

HRID 1296393Notes

Reaction equation

HRID 1296393 reaction equation
[Br:1][C:2]1[N:10]([CH2:11][O:12][CH2:13][CH3:14])[C:9]2[C:8](=[O:15])[NH:7][C:6](=[O:16])[N:5]([CH3:17])[C:4]=2[N:3]=1.[H-].[Na+].[C:20]([O:23][C@H:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28][Cl:29])(=[O:22])[CH3:21]>CS(C)=O>[C:20]([O:23][CH:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28][Cl:29])(=[O:22])[CH3:21].[C:20]([O:23][C@H:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28][N:7]1[C:8](=[O:15])[C:9]2[N:10]([CH2:11][O:12][CH2:13][CH3:14])[C:2]([Br:1])=[N:3][C:4]=2[N:5]([CH3:17])[C:6]1=[O:16])(=[O:22])[CH3:21]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 110194345-(R)-Acetoxy-1-chlorohexaneHCID 224991168-Bromo-7-ethoxymethyl-3-methylxanthine

Product 2

HCID 36180515-Acetoxy-1-chlorohexaneHCID 54041337(R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthineYield 149.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirring suspension of 8-bromo-7-ethoxymethyl-3-methylxanthine (1.52 g, 5.0 mmol) in anhydrous dimethylsulfoxide (20 ml) was added sodium hydride (144 mg, 6.0 mmol). The mixture was stirred at room temperature for 30 min and then (R)-5-acetoxy-1-chlorohexane (983 mg, 5.5 mmol) was added and the mixture was stirred at 70-75° C. 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, which is incorporated herein by reference. After 12 hours, the mixture was cooled to room temperature, quenched with saturated aqueous sodium chloride solution (100 ml) and extracted with ethyl acetate (3×50 ml). The combined extracts were washed with water (2×25 ml), with saturated aqueous sodium chloride solution (25 ml) and dried over magnesium sulfate. After evaporation of the solvent under reduced pressure, the product was purified by flash chromatography over silica gel eluting with ethyl acetate to provide (R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthine (1.83 g, 82% yield) as a beige solid.

Workup

  1. stirringthe mixture was stirred at 70-75° C
  2. waitAfter 12 hours
  3. temperaturethe mixture was cooled to room temperature
  4. customquenched with saturated aqueous sodium chloride solution (100 ml)
  5. extractionextracted with ethyl acetate (3×50 ml)
  6. washThe combined extracts were washed with water (2×25 ml), with saturated aqueous sodium chloride solution (25 ml)
  7. dry with materialdried over magnesium sulfate
  8. customAfter evaporation of the solvent under reduced pressure
  9. customthe product was purified by flash chromatography over silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-fdd9593426534eab83d4fd91042da4f0
Source dataset
uspto-grants-2007_07
Patent number
US07247630B2

Reaction notes

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