1-bromo-3-(bromomethyl)-5-chlorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G3. A mixture of 1-bromo-3-(bromomethyl)-5-chlorobenzene (6 g, ˜21 mmol) and potassium phthalimide (3.15 g, 17 mmol) in DMF (50 ml) was heated at 120° C. for 2 hours. After cooled down, a white solid precipitated. The solid was filtered and washed with ethanol, then dried in vacuum. 2-(3-Bromo-5-chlorobenzyl)isoindoline-1,3-dione (5.1 g, 85%) was obtained as white solid. 1H NMR (DMSO-d6): δδ3.72 (s, 2H), 7.43 (s, 1H), 7.51 (s, 1H), 7.52 (s, 1H), 7.84, 7.86 (d, 2H), 8.05, 8.07 (d, 2H). After cooled down a white solid precipitated The solid was filtered washed with ethanol dried in vacuum

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G3. A mixture of 1-bromo-3-(bromomethyl)-5-chlorobenzene (6 g, ˜21 mmol) and potassium phthalimide (3.15 g, 17 mmol) in DMF (50 ml) was heated at 120° C. for 2 hours. After cooled down, a white solid precipitated. The solid was filtered and washed with ethanol, then dried in vacuum. 2-(3-Bromo-5-chlorobenzyl)isoindoline-1,3-dione (5.1 g, 85%) was obtained as white solid. 1H NMR (DMSO-d6): δδ3.72 (s, 2H), 7.43 (s, 1H), 7.51 (s, 1H), 7.52 (s, 1H), 7.84, 7.86 (d, 2H), 8.05, 8.07 (d, 2H). After cooled down a white solid precipitated The solid was filtered washed with ethanol dried in vacuum

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G2. The mixture of 3-bromo-5-chlorotoluene (9 g, 43.8 mmol), NBS (8.19 g, 46 mmol), and AIBN (200 mg) in carbon tetrachloride (50 mL) was heated at 80° C. for 3 hours. The resulting mixture was run through a silicon gel column with dichloromethane as the eluant. The fraction was collected and solvent was removed by rotovap, crude 1-bromo-3-(bromomethyl)-5-chlorobenzene (3) was obtained as a brown residue and used in the next step without further purification. The fraction was collected solvent was removed by rotovap

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.5 grams of 7-methoxy-1,4-benzoxazin-3-one (2.8 mmole) was dissolved in 10 ml of dimethylformamide and cooled in an ice bath. 0.17 grams (3.5 mmole) of sodium hydride (60% wt. inn oil) was added, and after 5 minutes 0.8 grams (2.9 mmole) of 3-bromo-5-chloro-benzylbromide was added all at once. The mixture was stirred at ice bath temperature for 1 hour, and then quenched by addition of 1% hydrochloric acid. The product was extracted with ethyl acetate, that was evaporated under reduced pressure to give an oil which was chromatographed via medium pressure eluting with 10% ethyl acetate in hexanes to yield 0.9 grams of 4-(3-bromo-5-chloro-benzyl)-7-methoxy-4H-benzo[1,4]oxazin-3-one as a white solid. cooled in an ice bath quenched by addition of 1% hydrochloric acid The product was extracted with ethyl acetate, that was evaporated under reduced pressure to give an oil which was chromatographed via medium pressure eluting with 10% ethyl acetate in hexanes

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.5 grams of 7-methoxy-1,4-benzoxazin-3-one (2.8 mmole) was dissolved in 10 ml of dimethylformamide and cooled in an ice bath. 0.17 grams (3.5 mmole) of sodium hydride (60% wt. inn oil) was added, and after 5 minutes 0.8 grams (2.9 mmole) of 3-bromo-5-chloro-benzylbromide was added all at once. The mixture was stirred at ice bath temperature for 1 hour, and then quenched by addition of 1% hydrochloric acid. The product was extracted with ethyl acetate, that was evaporated under reduced pressure to give an oil which was chromatographed via medium pressure eluting with 10% ethyl acetate in hexanes to yield 0.9 grams of 4-(3-bromo-5-chloro-benzyl)-7-methoxy-4H-benzo[1,4]oxazin-3-one as a white solid. cooled in an ice bath quenched by addition of 1% hydrochloric acid The product was extracted with ethyl acetate, that was evaporated under reduced pressure to give an oil which was chromatographed via medium pressure eluting with 10% ethyl acetate in hexanes

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G3. A mixture of 1-bromo-3-(bromomethyl)-5-chlorobenzene (6 g, ˜21 mmol) and potassium phthalimide (3.15 g, 17 mmol) in DMF (50 ml) was heated at 120° C. for 2 hours. After cooled down, a white solid precipitated. The solid was filtered and washed with ethanol, then dried in vacuum. 2-(3-Bromo-5-chlorobenzyl)isoindoline-1,3-dione (5.1 g, 85%) was obtained as white solid. 1H NMR (DMSO-d6): δ3.72 (s, 2H), 7.43 (s, 1H), 7.51 (s, 1H), 7.52 (s, 1H), 7.84,7.86 (d,2H), 8.05,8.07 (d,2H). After cooled down a white solid precipitated The solid was filtered washed with ethanol dried in vacuum

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G2. The mixture of 3-bromo-5-chlorotoluene (9 g, 43.8 mmol), NBS (8.19 g, 46 mmol), and AIBN (200 mg) in carbon tetrachloride (50 mL) was heated at 80° C. for 3 hours. The resulting mixture was run through a silicon gel column with dichloromethane as the eluant. The fraction was collected and solvent was removed by rotovap, crude 1-bromo-3-(bromomethyl)-5-chlorobenzene (3) was obtained as a brown residue and used in the next step without further purification. The fraction was collected solvent was removed by rotovap

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G3. A mixture of 1-bromo-3-(bromomethyl)-5-chlorobenzene (6 g, ˜21 mmol) and potassium phthalimide (3.15 g, 17 mmol) in DMF (50 ml) was heated at 120° C. for 2 hours. After cooled down, a white solid precipitated. The solid was filtered and washed with ethanol, then dried in vacuum. 2-(3-Bromo-5-chlorobenzyl)isoindoline-1,3-dione (5.1 g, 85%) was obtained as white solid. 1H NMR (DMSO-d6): δδ3.72 (s, 2H), 7.43 (s, 1H), 7.51 (s, 1H), 7.52 (s, 1H), 7.84, 7.86 (d, 2H), 8.05, 8.07 (d, 2H). After cooled down a white solid precipitated The solid was filtered washed with ethanol dried in vacuum

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G2. The mixture of 3-bromo-5-chlorotoluene (9 g, 43.8 mmol), NBS (8.19 g, 46 mmol), and AIBN (200 mg) in carbon tetrachloride (50 mL) was heated at 80° C. for 3 hours. The resulting mixture was run through a silicon gel column with dichloromethane as the eluant. The fraction was collected and solvent was removed by rotovap, crude 1-bromo-3-(bromomethyl)-5-chlorobenzene (3) was obtained as a brown residue and used in the next step without further purification. The fraction was collected solvent was removed by rotovap

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.5 grams of 7-methoxy-1,4-benzoxazin-3-one (2.8 mmole) was dissolved in 10 ml of dimethylformamide and cooled in an ice bath. 0.17 grams (3.5 mmole) of sodium hydride (60% wt. inn oil) was added, and after 5 minutes 0.8 grams (2.9 mmole) of 3-bromo-5-chloro-benzylbromide was added all at once. The mixture was stirred at ice bath temperature for 1 hour, and then quenched by addition of 1% hydrochloric acid. The product was extracted with ethyl acetate, that was evaporated under reduced pressure to give an oil which was chromatographed via medium pressure eluting with 10% ethyl acetate in hexanes to yield 0.9 grams of 4-(3-bromo-5-chloro-benzyl)-7-methoxy-4H-benzo[1,4]oxazin-3-one as a white solid. cooled in an ice bath quenched by addition of 1% hydrochloric acid The product was extracted with ethyl acetate, that was evaporated under reduced pressure to give an oil which was chromatographed via medium pressure eluting with 10% ethyl acetate in hexanes