Acetaldehyde → 1-(3-((tert-butyldimethysilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxyethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

HRID 2200745Notes

Reaction equation

HRID 2200745 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C:6](=[O:31])[N:5]([CH3:32])[C:4]=2[N:3]=1.C([Li])CCC.[CH:38](=[O:40])[CH3:39]>C1COCC1.O>[Si:24]([O:23][CH2:22][CH2:21][CH2:20][N:7]1[C:8](=[O:19])[C:9]2[N:10]([CH2:11][C:12]3[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=3)[C:2]([CH:38]([OH:40])[CH3:39])=[N:3][C:4]=2[N:5]([CH3:32])[C:6]1=[O:31])([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:25])[CH3:26]

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 904028568-bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione2×HCID 178418339Butyllithium

Product 1

HCID 904040471-(3-((tert-butyldimethysilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxyethyl)-3-methyl-1H-purine-2,6(3H,7H)-dioneYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Step 1 8-Bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.25 g, 0.46 mmol, intermediate 77) was dissolved in THF (5 mL) and cooled to −78° C. To the clear solution was added 2.5 M n-butyllithium in hexanes (0.20 mL, 0.51 mmol) dropwise. The reaction was stirred in the cold for 5 min and acetaldehyde (0.13 mL, 2.31 mmol) was added. The reaction was warmed to room temperature and stirred for 1 h. The reaction was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure to leave a golden oil. The oil was purified using two 1000 microns preparative TLC plates eluted with 50% ethyl acetate/hexanes. Target band was extracted with ethyl acetate and the solvent was removed under reduced pressure to give 1-(3-((tert-butyldimethysilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxyethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.052 g, 30% yield) as a clear oil. LCMS retention time=4.490 min and 97% purity, LCMS MH+ 507.

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. stirringstirred for 1 h
  3. extractionextracted with ethyl acetate (3×75 mL)
  4. dry with materialThe combined extracts were dried with magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customto leave a golden oil
  8. customThe oil was purified
  9. washeluted with 50% ethyl acetate/hexanes
  10. extractionTarget band was extracted with ethyl acetate
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-cb1bf42ce76543a0b7e113774b445837
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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