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

HRID 1835718Notes

Reaction equation

HRID 1835718 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][CH:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28]Cl)(=[O:22])[CH3:21]>CS(C)=O>[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

5

Reactant 3

HCID 24758Sodium hydrideHCID 36180515-Acetoxy-1-chlorohexaneHCID 224991168-Bromo-7-ethoxymethyl-3-methylxanthine

Product 1

HCID 54041337(R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthineYield 62.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

8-Bromo-7-ethoxymethyl-3-methylxanthine (prepared as described for CT12440) (3.03 g, 10 mmol) was added to a suspension of sodium hydride (264 mg, 11 mmol) in anhydrous dimethylsulfoxide (60 ml). After stirring for 30 minutes, (R) 5-acetoxy-1-chlorohexane (1.963 g, 11 mmol) was added and the mixture was heated at 70-80° C. for 12 hours. After cooling to room temperature, the reaction was quenched by the addition of water (150 ml) and extracted with 10% methanol-ethyl acetate (3×25 ml). The combined extracts were washed with water (2×50 ml), with saturated aqueous sodium chloride solution (50 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with 30% ethyl acetate-hexane to provide (R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthine (2.77 g).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was quenched by the addition of water (150 ml)
  3. extractionextracted with 10% methanol-ethyl acetate (3×25 ml)
  4. washThe combined extracts were washed with water (2×50 ml), with saturated aqueous sodium chloride solution (50 ml)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel eluting with 30% ethyl acetate-hexane

Sources & evidence

ORD record
ord-920fc64e74db41b3852bf4c467794076
Source dataset
uspto-grants-2004_08
Patent number
US06774130B2

Reaction notes

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