Sodium hydride → (R)-1-(5-acetoxyhexyl)-7-benzyl-3,8-dimethylxanthine
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][C@H:27]([CH3:33])[CH2:28][CH2:29][CH2:30][CH2:31]Cl)(=[O:25])[CH3:24]>CS(C)=O>[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
5
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 DMSO (20 ml) and stirred for 30 min. (R)-5-acetoxy-1-chlorohexane (357 mg) (prepared according to Kline et al. U.S. Pat. No. 5,629,423 (1997)) was added and the mixture was heated at 70-80° C. for 12 h. After cooling to room temperature, the reaction was 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), with saturated aqueous sodium chloride solution (50 ml), dried over magnesium sulfate and concentrated. The product was purified by flash chromatography (silica gel) eluting with ethyl acetate. Yield=638 mg.
Workup
- customprepared
- addition5,629,423 (1997)) was added
- temperatureAfter cooling to room temperature
- customthe reaction was quenched by the addition of water (50 ml)
- extractionextracted with ethyl acetate (3×75 ml)
- washThe combined extracts were washed with water (2×50 ml), with saturated aqueous sodium chloride solution (50 ml)
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
- customThe product was purified by flash chromatography (silica gel)
- washeluting with ethyl acetate
Sources & evidence
- ORD record
- ord-4f19d0c86fdb439cb02e2a63be4433b0
- Source dataset
- uspto-grants-2000_06
- Patent number
- US06075029
Reaction notes
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