Ethyl Acetate → (S)-1-(5-Acetoxyhexyl)-3-(2-furylmethyl)-7-pivaloyloxymethyl-8-methylxanthine

HRID 1421241Notes

Reaction equation

HRID 1421241 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:15]2[N:14]=[C:13]([CH3:16])[N:12]([CH2:17][O:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[C:11]=2[C:10](=[O:25])[NH:9][C:8]1=[O:26].[H-].[Na+].[C:29]([O:32][C@@H:33]([CH3:39])[CH2:34][CH2:35][CH2:36][CH2:37]Br)(=[O:31])[CH3:30].C(OCC)(=O)C>CS(C)=O>[C:29]([O:32][C@@H:33]([CH3:39])[CH2:34][CH2:35][CH2:36][CH2:37][N:9]1[C:10](=[O:25])[C:11]2[N:12]([CH2:17][O:18][C:19](=[O:24])[C:20]([CH3:22])([CH3:23])[CH3:21])[C:13]([CH3:16])=[N:14][C:15]=2[N:7]([CH2:6][C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)[C:8]1=[O:26])(=[O:31])[CH3:30]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 187805583-(2-Furylmethyl)-7-pivaloyloxymethyl-8-methylxanthineHCID 54040544(S)-5-acetoxy-1-bromohexane

Product 1

HCID 15481614(S)-1-(5-Acetoxyhexyl)-3-(2-furylmethyl)-7-pivaloyloxymethyl-8-methylxanthineYield 47.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirring solution of 3-(2-Furylmethyl)-7-pivaloyloxymethyl-8-methylxanthine (0.65 g, 1.8 mmol) in dimethyl sulfoxide (20 ml) was added sodium hydride in one portion. After 30 minutes, (S)-5-acetoxy-1-bromohexane (0.48 g, 2.16 mmol) was added neat. After stirring at ambient temperature for 20 hours, the reaction was quenched by addition of water (70 ml) and then extracted with ethyl acetate (3×35 ml). The combined extracts were washed with saturated aqueous sodium chloride solution (30 ml), dried over sodium sulfate and concentrated to give a yellow oil. Flash chromatography on silica gel eluting with ethyl acetate gave (S)-1-(5-Acetoxyhexyl)-3-(2-furylmethyl)-7-pivaloyloxymethyl-8-methylxanthine (0.43 g) as a yellow oil. The product oil was dissolved in methanol (20 ml) and treated with a sodium methoxide solution (25 wt. % in MeOH, 0.98 ml, 4.3 mmol). After stirring at ambient temperature for 48 hours, the solution was diluted with ethyl acetate (40 ml) and quenched with water (20 ml). The organic phase was washed with saturated aqueous sodium chloride solution (20 ml), dried over sodium sulfate and concentrated to give a yellow solid. Column chromatography on silica gel eluting with 10% methane ethyl acetate gave (S)-3-(2-furylmethyl)1-(5-hydroxyhexyl)-8-methylxanthine CT2412S (80 mg) as a white solid.

Workup

  1. customthe reaction was quenched by addition of water (70 ml)
  2. extractionextracted with ethyl acetate (3×35 ml)
  3. washThe combined extracts were washed with saturated aqueous sodium chloride solution (30 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customto give a yellow oil

Sources & evidence

ORD record
ord-3325e45779b94f8fb506e9710a7c5074
Source dataset
uspto-grants-2000_06
Patent number
US06075029

Reaction notes

Loading…