Dimethylformamide → HCID 54125089, compound

HRID 1600948Notes

Reaction equation

HRID 1600948 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[C:11]([OH:16])[CH:12]=3)[CH:7]=2)[CH2:3][CH2:2]1.[H-].[Na+].[CH3:19][N:20]([CH3:23])C=O>>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]3[C:13](=[CH:14][CH:15]=2)[CH:12]=[C:11]([O:16][CH2:15][C@H:6]([OH:5])[CH2:7][CH2:8][C:9]2[CH:23]=[N:20][CH:19]=[CH:11][CH:10]=2)[CH:10]=[CH:9]3)[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 21830628HCID 21830628, compound

Product 1

HCID 54125089HCID 54125089, compound

Conditions

Temperature
20 °C

Procedure

A solution of 2-cyclopropylmethoxy-6-hydroxynaphthalene (0.270 g) in anhydrous N,N-dimethylformamide (10 ml) was added dropwise to sodium hydride (60% dispersion in mineral oil, 0.457 g) that had been previously washed with isohexane (2 ml) under a nitrogen atmosphere. After stirring at 20° C. for 20 minutes a solution of (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-pyridyl)-1-(4-toluenesulfonyloxy)butane (0.46 g) in anhydrous N,N-dimethylformamide (2 ml) was added and the mixture stirred at 60° C. for 90 minutes. After cooling the reaction was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (50 ml) and treated with tetrabutylammonium fluoride hydrate (0.48 g). After 1 hour the solution was diluted with water and extracted with ether. The organic extract was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica eluting with dichloromethane:methanol (24:1) to give the title compound as a solid (0.124 g) which was recrystallised from ethyl acetate/isohexane.

Workup

  1. washhad been previously washed with isohexane (2 ml) under a nitrogen atmosphere
  2. additionwas added
  3. stirringthe mixture stirred at 60° C. for 90 minutes
  4. temperatureAfter cooling the reaction
  5. additionwas poured into saturated aqueous sodium hydrogen carbonate solution
  6. extractionextracted with ether
  7. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in tetrahydrofuran (50 ml)
  11. additiontreated with tetrabutylammonium fluoride hydrate (0.48 g)
  12. additionAfter 1 hour the solution was diluted with water
  13. extractionextracted with ether
  14. extractionThe organic extract
  15. dry with materialwas dried over anhydrous magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by column chromatography over silica eluting with dichloromethane:methanol (24:1)

Sources & evidence

ORD record
ord-cd5e8832072a41639e2fd15004267d76
Source dataset
uspto-grants-1999_11
Patent number
US05977105

Reaction notes

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