2-chloro-4-fluoro-3-methylbenzonitrile

Cool a solution of diisopropylamine (80.6 niL, 0.575 mol) in THF (1 L) to about -5 Preparation 12-Chloro-4-fluoro-3-methyl-benzonitrileTo a solution of diisopropylamine (474 mL, 3.35 mol) in anhydrous THF (5.8 L) at-5 °C under a nitrogen atmosphere is added dropwise 2.5 M n-butyllithium in hexanes (1.24 L, 3.10 mol) over 3 h and the resulting mixture is stirred at -5 °C for one additional hour. The LDA solution is added dropwise to a solution of 2-chloro-4-fluoro-benzonitrile (400 g, 2.58 mol) in anhydrous THF (5.8 L) at -70 °C over 6 h and then stirred at -70 °C overnight. lodomethane (643 mL, 10.32 mol) is added dropwise over 2.5 h and the temperature is raised to -5 °C for 17 h. Saturated aqueous ammonium chloride (3 L) is added. The solution is diluted with water (3.5 L) and extracted with diethyl ether (2 x 2 L). The organic phases are separated, combined, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a black solid. The solid is purified through a silica gel pad eluting withEtOAc/hexanes (1/40) to obtain the title compound (323 g, 74percent). 1H NMR (300 MHz, CDCls) δ 7.08 (dd, J= 8.6, 8.6 Hz, 1H), 7.54 (dd, J= 8.6, 5.6 Hz, 1H), 2.36 (d, J= 2.4 Hz, 3H).Example 8 2-Chloro-4-fluoro-3-methylbenzonitrile (198RL18) 3-Bromo-2-chloro-6-fluorotoluene (7.0 g, 31 mmol), zinc cyanide (3.7 g, 31 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.81 g, 1.56 mmol) was added to a flask under argon atmosphere. Dry DMF (35 mL) was added and the reaction mixture was stirred under argon at 120° C. The reaction was monitored by GC-MS and full conversion was observed after 2 hours. The mixture was diluted with dichloromethane (300 mL), washed with water (100 mL) and 4percent magnesium sulfate solution (100 mL), dried over magnesium sulphate, filtered, and evaporated to give a clear oil. The product was further purified by column chromatography on silica gel using n-heptane/ethyl acetate (9:1) giving a white solid (3.79 g, 71percent). Example 3

Molecular Weight:169.58
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Exact Mass:169.0094550
Monoisotopic Mass:169.0094550
Topological Polar Surface Area:23.8
Heavy Atom Count:11
Complexity:186
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes