Acetone → 2-(1,2,3,4-Tetrahydroisoquinolin-2-yl)ethoxyl-2-methoxybenzaldehyde

HRID 1166774Notes

Reaction equation

HRID 1166774 reaction equation
BrCCO[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[C:7]([O:13][CH3:14])[CH:6]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25][NH:24]1.[CH3:33][C:34](C)=[O:35]>>[CH2:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25][N:24]1[CH2:33][CH2:34][O:35][C:6]1[C:7]([O:13][CH3:14])=[C:8]([CH:11]=[CH:12][CH:5]=1)[CH:9]=[O:10]

Participants

6

Reactant 5

HCID 180AcetoneHCID 4875Potassium IodideHCID 70461,2,3,4-TetrahydroisoquinolineHCID 11430Potassium CarbonateHCID 229991114-(2-Bromoethoxy)-2-methoxybenzaldehyde

Product 1

HCID 539501422-(1,2,3,4-Tetrahydroisoquinolin-2-yl)ethoxyl-2-methoxybenzaldehyde

Procedure

The above 4-(2-bromoethoxy)-2-methoxybenzaldehyde (16.8 g, 65 mmol) ([building block 2]) was dissolved in acetone (300 ml) and potassium carbonate (44.9 g, 0.33 mol), potassium iodide (2 g) were added followed by addition of 1,2,3,4-tetrahydroisoquinoline (9.07 g, 72 mmol). The resulting mixture was stirred vigorously at reflux temperature for 16 hours. After cooling, the mixture was filtered and the inorganic precipitate was washed with acetone (100 ml). The combined acetone filtrates were concentrated in vacuo. The residue was dissolved in ethyl acetate (50 ml) and washed with water (2×20 ml) saturated sodium chloride (20 ml), dried over MgSO4 and concentrated in vacuo. The residue (23 g) was purified by column chromatography on silica gel (400 g) eluting first with a mixture of ethyl acetate and heptane (1:1, 2 liters) then with a mixture of ethyl acetate and heptane (2:1, 5 liters) to afford 12 9 (60%) of 4-[2-(1,2,3,4-tetrahydroisoquinolin-2-yl)ethoxyl-2-methoxybenzaldehyde as a solid.

Workup

  1. temperatureat reflux temperature for 16 hours
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered
  4. washthe inorganic precipitate was washed with acetone (100 ml)
  5. concentrationThe combined acetone filtrates were concentrated in vacuo
  6. dissolutionThe residue was dissolved in ethyl acetate (50 ml)
  7. washwashed with water (2×20 ml) saturated sodium chloride (20 ml)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue (23 g) was purified by column chromatography on silica gel (400 g)
  11. washeluting first with a mixture of ethyl acetate and heptane (1:1, 2 liters)
  12. additionwith a mixture of ethyl acetate and heptane (2:1, 5 liters)

Sources & evidence

ORD record
ord-9cf77d8e13874329896bf687963d626e
Source dataset
uspto-grants-2003_09
Patent number
US06613942B1

Reaction notes

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