Reaction #685064

Reaction equation

acrolein diethylacetal

4-bromo-3-chloro anisole

KCl

K2CO3

→

3-(2-chloro-4-methoxy-phenyl)-propenal

Yield 49.6%

Solvents

DMF

Conditions

Workup

1. 1
   OtherN2 was bubbled through the mixture and Pd(OAc)2 (1.1 g, 4. mmol, 3 mol %)
2. 2
   workup.ADDITIONwas added
3. 3
   Temperaturethen cooled in an ice-bath
4. 4
   workup.ADDITION300 mL of water was then added
5. 5
   OtherThe ice-bath was removed
6. 6
   ExtractionThe solution was extracted with ethyl acetate once
7. 7
   WashThe combined organic layer washed with water, brine
8. 8
   Dryingdried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated
11. 11
    Otherto provide the crude product which
12. 12
    Otherwas recrystallized from hot ethyl acetate-hexanes

Procedure

To a mixture of 4-bromo-3-chloro anisole (35 g, 0.159 mol), KCl (11.9 g, 0.160 mol, 1 eq.), K2CO3 (33 g, 0.238 mol, 1.5 eq) in 400 mL DMF in a sealed tube was added acrolein diethylacetal (73 mL, 0.479 mol, 3 eq.) and Bu4NOAc (96 g, 0.318 mol, 2 eq.). N2 was bubbled through the mixture and Pd(OAc)2 (1.1 g, 4. mmol, 3 mol %) was added. The reaction mixture was heated in an oil bath for 6 hr at 100° C. then cooled in an ice-bath. 300 mL of water was then added, followed by 500 mL of 1N HCl. The ice-bath was removed and the mixture was stirred for 30 min. The solution was extracted with ethyl acetate once then with diethyl ether 3 times. The combined organic layer washed with water, brine, dried over MgSO4, filtered and concentrated to provide the crude product which was recrystallized from hot ethyl acetate-hexanes to provide 15.5 g of crystalline 3-(2-chloro-4-methoxy-phenyl)-propenal. The mother liquor was concentrated and chromatographed with 10% ethyl acetate to provide another 5.6 g of 3-(2-chloro-4-methoxy-phenyl)-propenal.

Source