Sodium hydride → (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine

HRID 1296411Notes

Reaction equation

HRID 1296411 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]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30][Br:31])(=[O:24])[CH3:23]>CS(C)=O>[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30][Br:31])(=[O:24])[CH3:23].[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30][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)[CH:9]=[N:10][C:11]=2[N:12]([CH3:19])[C:13]1=[O:18])(=[O:24])[CH3:23]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 6856307-Benzyl-3-methylxanthineHCID 12619445(R)-5-Acetoxy-1-bromohexane

Product 2

HCID 12619445(R)-5-Acetoxy-1-bromohexaneHCID 53701360(R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthineYield 144%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirring suspension of 7-benzyl-3-methylxanthine (11.1 g, 43.2 mmol) in dimethyl sulfoxide (100 ml) was added 95% sodium hydride (1.24 g, 52 mmol) in one portion. After stirring for 30 minutes, (R)-5-acetoxy-1-bromohexane (8.1 g, 45.3 mmol) was added neat. The (R)-5-Acetoxy-1-bromohexane was prepared according to methods described in U.S. Pat. No. 6,075,029 issued to Klein, J. P., Kumar, A. M., and Woodson, P on Jun. 13, 2000, which is incorporated herein by reference. After stirring at 80° C. for 16 hours and cooled to room temperature, the reaction was quenched by addition of water (350 ml) and extracted with ethyl acetate (5×50 ml). The combined extracts were washed with saturated aqueous sodium bicarbonate solution (50 ml), with saturated aqueous sodium chloride solution (50 ml) and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave a residue which was purified by flash chromatography on silica gel eluting with ethyl acetate to give (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine (13.0 g, 76% yield).

Workup

  1. stirringAfter stirring at 80° C. for 16 hours
  2. customthe reaction was quenched by addition of water (350 ml)
  3. extractionextracted with ethyl acetate (5×50 ml)
  4. washThe combined extracts were washed with saturated aqueous sodium bicarbonate solution (50 ml), with saturated aqueous sodium chloride solution (50 ml)
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of the solvent under reduced pressure
  7. customgave a residue which
  8. customwas purified by flash chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-71bb64e0253b4cb8ae0320fbe0d86bef
Source dataset
uspto-grants-2007_07
Patent number
US07247630B2

Reaction notes

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