2-Bromo-5-chlorobenzonitrile

off-white crytalline

An alternative synthesis of compound 1-2 follows: To a solution of 3-chlorobenzonitrile 1-1 (50 g, 360 mmol) in trifluoroacetic acid (180 mL) was added sulfuric acid (24 mL) and then 1, 3-dibromo-5, 5-dimethylhydantoin (67 g, 234 mmol) in portions over 8 minutes. The reaction temperature was allowed to reach 31° C. and then cooling was applied to bring the temperature to 24° C. After a 6 hour age, the heterogeneous reaction was cooled to 10° C. and water (250 mL) was added. Following a 10 minute age, the reaction was filtered and the product cake was washed twice with water (250 and 100 mL) to afford a white solid (52.4 g, 63percent). 1H NMR (CDCl3, 400 MHz) 6 7.64-7.62 (m, 2H), 7.44 (dd, J=8.6, 2.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ134.2, 134.1, 133.9, 133.8, 123.3, 117.2, 115.8An alternative synthesis of compound 1-2 follows: To a solution of 3-chlorobenzonitrile 1-1 (50 g, 360 mmol) in trifluoroacetic acid (180 mL) was added sulfuric acid (24 mL) and then 1, 3-dibromo-5, 5-dimethylhydantoin (67 g, 234 mmol) in portions over 8 minutes. The reaction temperature was allowed to reach 31 C. and then cooling was applied to bring the temperature to 24 C. After a 6 hour age, the heterogeneous reaction was cooled to 10 C. and water (250 mL) was added. Following a 10 minute age, the reaction was filtered and the product cake was washed twice with water (250 and 100 mL) to afford a white solid (52.4 g, 63%). 1H NMR (CDCl3, 400 MHz) 6 7.64-7.62 (m, 2H), 7.44 (dd, J=8.6, 2.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz) delta134.2, 134.1, 133.9, 133.8, 123.3, 117.2, 115.8To a 400 L glass lined vessel was charged 1, 3-dibromo-5, 5-dimethyl-hydantoin (DBH) (10.88 kg, 38.6 mol), followed by methane sulfonic acid (111.4 kg). The resulting slurry was warmed to 35 C. to form a DBH solution. [0306] To a separate 400 L vessel was charged 3-chlorobenzonitrile 1-1 (8.050 kg, 58.5 mol, Acros, Lancaster) melt and cyclohexane (1.8 L total), followed by methanesulfonic acid (47.6 kg) to form a benzonitrile solution, which was warmed to 25-30 C. to dissolve any solids. The DBH solution was added to the benzonitrile solution over a period of about 30 minutes with fast agitation while maintaining a batch temperature of <30 C. The empty DBH solution containing vessel was rinsed with methane sulfonic acid (5.0 kg) and the rinse was added to the reaction mixture. The reaction was aged at 30 C. for 1 to 2 hours to affect reaction conversion >95 area % (tracked via HPLC assay). The reaction was then cooled to about 14 C. and slowly quenched with water (80.5 L) to maintain a temperature of <30 C. The reaction was then re-cooled to 20 C. and MTBE was added (208.5 kg) at <30 C. under agitation. The mixture was allowed to settle, the layers were separated and the aqueous layer was extracted with 101 kg of MTBE at 30 C., followed by 30 kg of MTBE. The organic layers were combined and washed with 50 kg 1.6 N NaOH, and 54 kg water, and then concentrated to 48 L, cooled and seeded (10 g of seed). Once a slurry formed, the concentration was resumed until a batch volume of 40 L was achieved. The resulting slurry was aged at 20 C. for 1.5 hours and then filtered. The cake was washed with 12 kg of 1:1 MTBE:cyclohexane (in 2 drops). The wet solids were dried in a filter dryer to give 1-2. 1H NMR (CDCl3, 400 MHz) delta 7.39 (d, J=2.2 Hz, 1H), 7.22 (dd, J=2.3, 8.4 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H)To a 150 L glass lined reactor equipped with an overhead stirrer, dropping funnel, nitrogen blanket, and thermal couple readout was charged

Molecular Weight:216.46
XLogP3:3
Hydrogen Bond Acceptor Count:1
Exact Mass:214.91374
Monoisotopic Mass:214.91374
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes