2-Fluoro-4-cyanobenzyl bromide

White to yellow fine crystalline powder

4-(bromomethyl)-3-fluorobenzonitrile: 3 -Fluoro-4-methylbenzonitrile (40 g, 296 mmol), NBS (63.2 g, 356 mmol) and benzoyl peroxide (3.6 g, 14.8 mmol) were taken up in carbon tetrachioride (490 mL) and refluxed for 16 h. The mixture was allowed to cool to room temperature and filtered. The filtrate was concentrated and purified via flash column chromatography (0-5percent EtOAc/hexanes) to give 4-(bromomethyl)-3-fluorobenzonitrile (35.4 g, 56percent).1, 2-Dichloroethane (151 kg) was charged to a suitable vessel along with 4-cyano-2-fluorotoluene (24 kg) and AIBN (2 kg). The mixture was heated to 7074° C. Once the batch temperature reached 70° C., N-bromosuccinimide (47.4 kg) was added in portions at the rate of 12 kg/h, maintaining the temperature at 7074° C. (it is important to control addition rate to avoid exothermic reaction). The mixture was sampled via GC detection after 24 kg of N-bromosuccinimide was added, and the reaction was heated at 70-74° C. until complete reaction was observed. The mixture was cooled to 0-5° C. and allowed to stand for 2 additional hours. The mixture was filtered, and the cake was washed with MTBE (24 kg). The filtrate was washed with water (3.x.65 kg). The organic layer was dried with sodium sulfate (10.3 kg) for 6 hours, filtered and the cake was washed with MTBE (24 kg). The solution was evaporated under reduced pressure, ethanol (12 kg) was added and the mixture was heated to 40-45° C., then cooled slowly to 0-5° C. while stirring to crystallize. The mixture was filtered and the cake was washed with cold ethanol (5 kg). The crude solid was recrystallized from petroleum ether, filtered and washed with petroleum ether (10 kg), giving the title compound 4-(bromomethyl)-3-fluorobenzonitrile as an off white solid (21 kg, 55percent yield). Method B. Example 30 Example 90 Step 1: To a cooled solution of Example 91 Preparation of 3-fluoro-4-(azidomethyl)benzonitrile (5-5) Sodium azide (Aldrich, 0.63 g, 9.8 mmol) was added to a solution of Example 31 Preparation of 3-fluoro-4-(azidomethyl)benzonitrile (41) Sodium azide (Aldrich, 0.63 g, 9.8 mmol) was added to a solution of Example 91 Preparation of 3-fluoro-4-(azidomethyl)benzonitrile (5-5) Sodium azide (Aldrich, 0.63 g, 9.8 mmol) was added to a solution of 2-d (200 mg, 0.72 mmol), A mixture of 5-(Trifluoromethyl)phenyl-1, 3-diol (0.42 g, 2.4 mmol),

Molecular Weight:214.03
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:212.95894
Monoisotopic Mass:212.95894
Topological Polar Surface Area:23.8
Heavy Atom Count:11
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes