Hydrogen Bromide → 3'-BROMO-5'-FLUOROBIPHENYL-2-CARBONITRILE

Temperature

3 °C

A warm solution of 5′-amino-3′-fluorobiphenyl-2-carbonitrile (4.5 g, 21 mmol) in 1,4-dioxane (20 mL) was treated with 48% hydrobromic acid (100 mL) and the resulting suspension stirred and cooled to 3° C. (internal temperature). A solution of sodium nitrite (1.7 g, 24 mmol) in water (4 mL) was then added dropwise over 20 min keeping the internal temperature <5° C. Stirring at <5° C. was continued for 2 h before adding a cooled (5° C.) solution of copper(I) bromide (9.1 g, 3 mmol) in 48% hydrobromic acid (30 mL). The resulting purple reaction mixture was stirred at 5° C. for 10 min then warmed to 50° C. for 20 min. The reaction was diluted with ice-cold water (500 mL) and extracted with ethyl acetate (2×200 mL). The organics were combined, washed with 5% aqueous sodium sulphite and saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica gel. Purification on silica gel, eluting with isohexane (containing 1% methanol) on a gradient of ethyl acetate (5-15%) afforded 5′-bromo-3′-fluorobiphenyl-2-carbonitrile as a white solid (5.52 g, 94%).

1. customthe internal temperature <5° C
2. stirringStirring at <5° C.
3. additionbefore adding
4. stirringThe resulting purple reaction mixture was stirred at 5° C. for 10 min
5. temperaturethen warmed to 50° C. for 20 min
6. extractionextracted with ethyl acetate (2×200 mL)
7. washwashed with 5% aqueous sodium sulphite and saturated aqueous ammonium chloride
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered and pre-adsorbed onto silica gel
10. customPurification on silica gel
11. washeluting with isohexane (containing 1% methanol) on a gradient of ethyl acetate (5-15%)

ORD record

ord-808c2a4c3aaf4a2aa34ab0e5b282f3b5

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06960598B2