2-Fluoro-4-methylbenzonitrile

Off white crystalline

Preparation of 2-fluoro-4-methyIbenzonitriIeA mixture of 1 -bromo-2~fluoro-4-methylbenzene (70 g, 370 mmol) and CuCN (50 g, 555 mmol) in DMF (300 mL) was heated at reflux for 24 h. After cooling to RT, concentrated aqueous ammonia (300 mL) and diethyl ether (200 mL) were added and the mixture stirred for 1 h. The mixture was extracted with diethyl ether (3 x 200 mL). The combined organic layers were washed with brine (3 x 200 mL) and dried over sodium sulfate. Solvent was removed in vacuo to give the product (44 g, 88percent) as pale yellow solid. MS (M+H)a) 2-Fluoro-4-methylbenzonitrile A solution of sodium nitrite (4.22 g, 61.16 mmol) in water (40 mL) was added slowly to a stirred suspension of (2-fluoro-4-methylphenyl)amine (4.60 mL, 40.73 mmol) in hydrogen chloride (1M, 340 mL) at -5 °C, and the mixture was stirred at this temperature. After 10 minutes, sodium bicarbonate was added until the pH was 7-8. The reaction mixture was added slowly to a stirred solution of cyanocopper (12.22 g, 136.44 mmol) and potassium cyanide (8.10 g, 124.39 mmol) in water (150 mL). The reaction was warmed to 60 °C. After heating for 2 hours, ethyl acetate was added to the mixture and the aqueous layer was extracted with more ethyl acetate. The organic layer was washed with brine, dried (NaINTERMEDIATE 10; rV-Cyclopropyl-7-iodo-6-methyl-1 , 2-benzisoxazol-3-aminea) 2-Fluoro-4-methylbenzonitrile; A solution of sodium nitrite (4.22 g, 61.16 mmol) in water (40 mL) was added slowly to a stirred suspension of (2-fluoro-4-methylphenyl)amine (4.60 mL, 40.73 mmol) in hydrogen chloride (1M, 340 mL) at -5 °C, and the mixture was stirred at this temperature. After 10 minutes, sodium bicarbonate was added until the pH was 7-8. The reaction mixture was added slowly to a stirred solution of cyanocopper (12.22 g, 136.44 mmol) and potassium cyanide (8.10 g, 124.39 mmol) in water (150 mL). The reaction was warmed to 60 °C. After heating for 2 hours, ethyl acetate was added to the mixture and the aqueous layer was extracted with more ethyl acetate. The organic layer was washed with brine, dried (Na3-fluoro-4-nitrile toluene 1 (10 g, 74.07 mmol)Dissolved in chloroform 200mL, Add BPO 1g, stirring dissolved, NBS (19.77 g, 11.11 mmol) was added portionwise, Reflux 12h, Cooling, the reaction solution with saturated aqueous solution of sodium bicarbonate 3 times wash, Wash the amount of water 3 times, the amount of saturated salt water washed 3 times, evaporation of the solvent under reduced pressure, column chromatography was pale yellow liquid 14.00g, yield88.79%.To the solution of 83 A mixture of To a solution of 2-fluoro-4- methylbenzonitrile ( 135.0 g, 1 .0 mol) and BPO ( 1 3.5 g, 0.06 mol) in CHC13 (800 mL) was added NBS ( 178.0 g, 1 mol) in three portions. The mixture was stirred for 4 hrs at reflux. After cooling to room temperature, the solution was poured to a saturated aqueous NaHC03 and extracted with CH2CI2 (3 x 300 mL). The combined organic layer was washed with brine, dried over anhydrous Na2S04, and concentrated under reduced pressure to give the title compound (232 g) as a yellow viscous liquid, which was used directly in the next step without further purification.Step A. 4-Bromomethyl-2-fluoro-benzonitrile.

2-Fluoro-4-methylbenzonitrile is used in the synthesis of fluorobenzamidrazone thrombin inhibitors.

Molecular Weight:135.14
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Exact Mass:135.048427358
Monoisotopic Mass:135.048427358
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes