Toluene → HCID 15379742, compound

HRID 2270493Notes

Reaction equation

HRID 2270493 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Mg]Br)C.[C:10]([OH:13])(=O)C.[CH2:14]1[CH2:18][O:17][CH2:16][CH2:15]1.O.[C:20]1(C)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CCOCC>[O:17]=[C:18]1[CH2:23][CH2:24][C:25]2[C:15](=[C:16]([C:10]([C:2]3[NH:1][CH:5]=[CH:4][CH:3]=3)=[O:13])[CH:22]=[CH:21][CH:20]=2)[CH2:14]1

Participants

6

Reactant 4

HCID 1140Toluene2×HCID 8027PyrroleHCID 21877175AcOH THF waterHCID 178418443HCID 178418443, compound

Product 1

HCID 15379742HCID 15379742, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Pyrrole (3.17 ml) was dissolved in toluene (40 ml) and cooled to 0° while ethylmagnesium bromide (15.2 ml of a 3 M solution in ether) was added. This solution was allowed to warm to 25° and stirred for 30 minutes. A solution of methyl 1,2,3,4-tetrahydrospiro-2-[2-(1,3-dioxolane)]naphthalene-8-yl-carboxylate (5.15 g, 20.8 mmol) dissolved in toluene (20 ml) was added and the solution refluxed for 24 hours. The solution was cooled and quenched by the addition of saturated aqueous ammonium chloride. Ether (100 ml) was added and the solution extracted. The organic layer was washed with water (2×100 ml), saturated aqueous sodium bicarbonate (50 ml) and brine (50 ml). Drying over anhydrous sodium sulfate and solvent removal in vacuo afforded a dark oil. This was placed in a solution of acetic acid/THF/water (3:1:1) and heated to 50° for five hours. After cooling, the solvent was removed in vacuo and the residue placed on a flash silica gel column (3 cm×40 cm) and eluted with ethyl acetate/hexane (40:60) (added methylene chloride to dissolve crystallized product off the column. Solvent removal afforded 3.7 g of the title compound (74% yield) as light yellow needles (m.p. 174° C.).

Workup

  1. additionwas added
  2. temperatureto warm to 25°
  3. additionwas added
  4. temperaturethe solution refluxed for 24 hours
  5. temperatureThe solution was cooled
  6. customquenched by the addition of saturated aqueous ammonium chloride
  7. additionEther (100 ml) was added
  8. extractionthe solution extracted
  9. washThe organic layer was washed with water (2×100 ml), saturated aqueous sodium bicarbonate (50 ml) and brine (50 ml)
  10. dry with materialDrying over anhydrous sodium sulfate and solvent removal in vacuo
  11. customafforded a dark oil
  12. temperatureheated to 50° for five hours
  13. temperatureAfter cooling
  14. customthe solvent was removed in vacuo
  15. washeluted with ethyl acetate/hexane (40:60) (
  16. additionadded methylene chloride
  17. dissolutionto dissolve
  18. customcrystallized product off the column
  19. customSolvent removal

Sources & evidence

ORD record
ord-e6c450e1778247e6a6a2f2415bdec55f
Source dataset
uspto-grants-2001_12
Patent number
US06331636B1

Reaction notes

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