Reacción #9617

Ecuación de reacción

4-iodoformanilide

bis(pinacolato)diboron

potassium acetate

methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate

cesium carbonate

→

methyl 4-[4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

Disolventes

hexane

water

ethyl acetate

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe mixture was degassed by gently bubbling argon through the solution for 30 minutes at rt
2. 2
   Otro(2–3 hours)
3. 3
   TemperaturaAfter the mixture was cooled to rt
4. 4
   TemperaturaThe reaction mixture was then heated at 80° C. overnight under argon
5. 5
   TemperaturaThe mixture was cooled to rt
6. 6
   Otroto precipitate
7. 7
   OtroThe solids were removed by filtration
8. 8
   Lavadowashed with 500 mL water
9. 9
   workup.DISSOLUTIONThen the solids were dissolved in 500 mL methylene chloride
10. 10
    Otroblack particles were removed
11. 11
    LavadoThe filtrate was washed with 150 mL water (2×)
12. 12
    SecadoAfter the solution was dried over sodium sulfate
13. 13
    Concentraciónthe solution was concentrated under reduced pressure
14. 14
    Otroto afford a dark, brown residue
15. 15
    FiltraciónAfter filtration
16. 16
    Otrodrying

Procedimiento

To a 2-L three-necked round-bottomed flask were charged 4-iodoformanilide (30.0 g, 121 mmol, 1.0 eq), bis(pinacolato)diboron (30.8 g, 121 mmol, 1.0 eq), palladium acetate (0.82 g, 3.6 mmol, 3 mol %), potassium acetate (35.70 g, 364.3 mmol), and 500 mL N,N-dimethylformamide. The mixture was degassed by gently bubbling argon through the solution for 30 minutes at rt. The mixture was then heated at 80° C. under argon until the reaction was complete (2–3 hours). After the mixture was cooled to rt, methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (36.3 g, 121 mmol), cesium carbonate (59.4 g, 182 mmol), and palladium tetrakistriphenylphosphine (4.2 g, 3.6 mmol, 3 mol%) were added. The reaction mixture was then heated at 80° C. overnight under argon. The mixture was cooled to rt, and slowly diluted with water (1.5 L), which caused solid material to precipitate. The solids were removed by filtration, and washed with 500 mL water. Then the solids were dissolved in 500 mL methylene chloride, and black particles were removed by passing the solution through a pad of Celite®. The filtrate was washed with 150 mL water (2×). After the solution was dried over sodium sulfate, the solution was concentrated under reduced pressure to afford a dark, brown residue. The residue was stirred in ethyl acetate (200 mL) and hexane (200 mL) for 1 h. After filtration and drying, methyl 4-[4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate was obtained as a yellow solid (28.0 g, 68%). 1H NMR (CDCl3) δ 8.42 (d, J=2 Hz, 1H), 7.98 (d, J=8 Hz, 2H), 7.62 (m, 6H), 3.70 (s, 3H), 3.33 (s, 2H), 1.35 (s, 6H) and 40% tautomer; ESI-MS m/z 340.1 (MH+).

Fuente