Water → 1-(3-(R)-methyl-7-methyloct-6-enyl)-3,7-dimethylxanthine

HRID 1954113Notes

Reaction equation

HRID 1954113 reaction equation
[H-].[Na+].[NH:3]1[C:14](=[O:15])[C:13]2[N:11]([CH3:12])[CH:10]=[N:9][C:8]=2[N:6]([CH3:7])[C:4]1=[O:5].[CH2:16](Br)[CH2:17][C@@H:18]([CH2:20][CH2:21][CH:22]=[C:23]([CH3:25])[CH3:24])[CH3:19].O>CS(C)=O>[CH3:19][C@H:18]([CH2:20][CH2:21][CH:22]=[C:23]([CH3:25])[CH3:24])[CH2:17][CH2:16][N:3]1[C:14](=[O:15])[C:13]2[N:11]([CH3:12])[CH:10]=[N:9][C:8]=2[N:6]([CH3:7])[C:4]1=[O:5]

Participants

6

Reactant 4

HCID 962WaterHCID 5429TheobromineHCID 24758Sodium hydrideHCID 11042221(R)-(-)-Citronellyl bromide

Product 1

HCID 228614841-(3-(R)-methyl-7-methyloct-6-enyl)-3,7-dimethylxanthineYield 81.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

This example illustrates a synthesis of 1-(3-(R)-methyl-7-methyl-6,7-oxidooctyl)-3,7-dimethylxanthine (inventive compound no. 1588R). Sodium hydride(95%) (631 mg, 25 mmol) was added to a solution of theobromine (4.14 g, 23 mmol) in dimethylsulfoxide (75 mL). After 20 minutes of stirring, (R)(-)Citronellyl bromide (5.0 g, 22.8 mmol) was added. After 16 hours of stirring at room temperature, the reaction was poured into a separatory funnel containing 500 mL of water and extracted with dichloromethane (3×100 mL). The organic extracts were combined, washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product obtained was further purified by flash chromatography over silica gel using 30% petroleum ether/ethyl acetate eluant, yielding 5.9 g (81.5% yield) 1-(3-(R)-methyl-7-methyloct-6-enyl)-3,7-dimethylxanthine (inventive compound no. 1596R) as a yellowish oil. A solution of 1-(3-(R)-methyl-7-methyloct-6-enyl)-3,7-dimethylxanthine (318 mg, 1 mmol) and m-chloroperoxybenzoic acid (0.52 g; 1.5 mmol) (50% by wt) in dichloromethane (7 mL) was stirred for 5 hours. The reaction mixture was diluted with 40 mL of dichloromethane and washed successively with 20% aqueous sodium sulphite solution (10 mL), saturated sodium bicarbonate solution (10 mL), water and brine solutions. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product obtained was further purified by flash chromatography over silica gel using 5% petroleum ether/ethyl acetate eluant, yielding 0.253 g (76% yield) of 1-(3-(R)-methyl-7-methyl-6,7-oxidooctyl)-3,7-dimethylxanthine.

Workup

  1. stirringAfter 16 hours of stirring at room temperature
  2. additionthe reaction was poured into a separatory funnel
  3. extractionextracted with dichloromethane (3×100 mL)
  4. washwashed with water (100 mL) and brine (100 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product obtained
  8. customwas further purified by flash chromatography over silica gel using 30% petroleum ether/ethyl acetate eluant

Sources & evidence

ORD record
ord-983d1360e82e4b6da7e13a46e6c75ca0
Source dataset
uspto-grants-2000_09
Patent number
US06121270

Reaction notes

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