تفاعل #169964

معادلة التفاعل

2-bromo-4-fluorobenzonitrile

benzofuran-2-ylboronic acid

1,2-dimethoxyethane

Na2CO3

→

title compound

2-(Benzofuran-2-yl)-4-fluorobenzonitrile

المذيبات

EtOAc

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwas heated
2. 2
   workup.ADDITIONwas added
3. 3
   درجة الحرارةheating
4. 4
   درجة الحرارةAfter cooling
5. 5
   workup.DISSOLUTIONto dissolve the product
6. 6
   ترشيحThe mixture was filtered through celite
7. 7
   أخرىthe organic layer was separated
8. 8
   تجفيفdried (Na2SO4)
9. 9
   تركيزconcentrated under reduced pressure
10. 10
    workup.DISSOLUTIONThe residue was dissolved in minimum amount of CHCl3
11. 11
    أخرىSolvent was evaporated
12. 12
    أخرىthe residue was first purified by crystallisation from a mixture CHCl3/PE (98/2)
13. 13
    أخرىThe filtrate was purified by Combiflash chromatography (40 g column, 13 g Silica, gradient of eluent from PE to PE/EtOac 9/1)

الإجراء التجريبي

A mixture of 2-bromo-4-fluorobenzonitrile (515 g, 25.65 mmol), benzofuran-2-ylboronic acid (5.0 g, 30.8 mmol), 1,2-dimethoxyethane (25 mL) and 2M Na2CO3 (40 mL) was heated to reflux before Pd2(dba)3 (100 mg) was added and heating was continued for 5 h. After cooling to r.t, EtOAc (20 mL) was added to dissolve the product. The mixture was filtered through celite, the organic layer was separated, dried (Na2SO4) and concentrated under reduced pressure. The residue was dissolved in minimum amount of CHCl3 and passed through Silica. Solvent was evaporated and the residue was first purified by crystallisation from a mixture CHCl3/PE (98/2). The filtrate was purified by Combiflash chromatography (40 g column, 13 g Silica, gradient of eluent from PE to PE/EtOac 9/1) to give the title compound as light yellow solid purified by rinsing with PE to give at the end a white solid (5.15 g). This solid had to be purified an ultimate time by drying under vacuum at 80° C. for O/N. Finally, pure expected compound was obtained as a off-white solid in 59% yield (3.6 g); mp 123-124° C.; 1H NMR (270 MHz, CDCl3) 87.13 (1H, td, J=2.5 and 7.3 Hz, ArH), 7.30 (1H, t, J=7.7 Hz, ArH), 7-40 (1H, t, J=77 Hz, ArH), 7.56 (1H, d, J=7.7 Hz, ArH), 7.69 (1H, d, J=73 Hz, ArH), 7.76-7.86 (3H, m, ArH); Anal. Calcd. for C15H8FNO: C, 75.94, H, 3.40, N, 5.90. Found: C, 75 70, H, 3.37, N, 5.97%.

المصدر