Reaction #58896

Reaction equation

2,4-dihydroxybenzaldehyde

trifluoromethanesulfonic anhydride

sodium hydride

ortho-tolylboronic acid

sodium carbonate

pyridine

2-dimethylamino ethylchloride

→

3-(2-Dimethylamino-ethoxy)-2′-methyl-biphenyl-4-carbaldehyde

Solvents

water

DME

methylene chloride

toluene

Conditions

Workup

1. 1
   Otherthe temperature below 5° C
2. 2
   WashAfter 10 min the mixture was washed with water
3. 3
   Concentrationthe organic phase was concentrated under reduced pressure
4. 4
   TemperatureThe mixture was refluxed for 17 h under Argon
5. 5
   Extractionextracted with ethyl acetate
6. 6
   workup.DISSOLUTIONThe crude black oil (4.6 g) was dissolved in DMF (75 ml)
7. 7
   Temperaturethe mixture was heated at 80° C. for 3 days
8. 8
   WashThe mixture was washed with saturated sodium bicarbonate
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    Otherpurified by chromatography
11. 11
    WashThe resulting yellow oil was washed with hot heptane giving the product as relative pure oil (GC-MS)

Procedure

A solution of 2,4-dihydroxybenzaldehyde (27 mmol) in methylene chloride (10 ml) and pyridine (30 mmol) was slowly added trifluoromethanesulfonic anhydride (32 mmol) keeping the temperature below 5° C. After 10 min the mixture was washed with water and the organic phase was concentrated under reduced pressure. The crude brown oil (5 g), ortho-tolylboronic acid (20.4 mmol), sodium carbonate (55.5 mmol) and dichlorobis(triphenylphosphine)-palladium (II) (3 mol %) was dissolved in DME (50 ml) and water (20 ml). The mixture was refluxed for 17 h under Argon, cooled to room temperature and extracted with ethyl acetate. The crude black oil (4.6 g) was dissolved in DMF (75 ml) and sodium hydride (60% in oil, 22.5 mmol) was slowly added. A solution of 2-dimethylamino ethylchloride (22.5 mmol) in toluene (120 ml) was added and the mixture was heated at 80° C. for 3 days. The mixture was washed with saturated sodium bicarbonate, concentrated under reduced pressure and purified by chromatography. The resulting yellow oil was washed with hot heptane giving the product as relative pure oil (GC-MS). 1H-NMR (DMSO-d6) δ 10.41 (s, 1H), 7.74 (d, 2H), 7.66-7.55 (m, 1H), 7.36-6.79 (m, 4H), 4.27 (t, 2H), 2.70 (t, 2H), 2.27 (s, 3H), 2.23 (s, 6H).

Source