1,3-Dibromo-5,5-dimethylhydantoin → Methyl 5-(bromomethyl)-2-nitrobenzoate

Temperature

75 °C

A mixture of 5-methyl-2-nitro-benzoic acid methyl ester (93.95 g, 481.35 mmol), 1,3-dibromo-5,5-dimethylhydantoin (75.70 g, 264.74 mmol), in methyl acetate (550 mL) was heated at 78° C. for 40 minutes while stirred with a mechanical stirrer. Then a solution of 2,2′-azobisisobutyro-nitrile (3.95 g, 24.07 mmol) in methyl acetate (80 mL) was added, and the mixture was heated at about 75° C. for 13 hours. The mixture was allowed to cooled to 15° C. and stirred for 2 hours to age the precipitate. The suspension was filtered, washed with 10° C. methyl acetate (2×50 mL) to give a brown filtrate. To the filtrate, was added heptane (500 mL). The organic layer was washed with 2% brine (2×500 mL) and water (2×500 mL), and concentrated to about 2 volumes. To the mixture, was added t-butyl methyl ether (or MTBE, 300 mL). The mixture was heated at about 70° C. for 15 minutes, cooled to about 53° C. over one hour, seeded with the product (about 250 mg, or simply re-crystallized) at 45° C., then at 20-25° C., while blowing nitrogen with a glass pipette overnight. The resulting solid was filtered via a medium pore-sized funnel, washed with a pre-cooled 10° C. mixed solvent of heptane/MTBE (1/2 vol/vol) and suction dried in hood overnight to give 5-bromomethyl-2-nitro-benzoic acid methyl ester as an off-white solid (58.3 g, 44.0% yield). The solid was used in the next step without further purification.

1. temperatureto cooled to 15° C.
2. stirringstirred for 2 hours to age the precipitate
3. filtrationThe suspension was filtered
4. washwashed with 10° C. methyl acetate (2×50 mL)
5. customto give a brown filtrate
6. washThe organic layer was washed with 2% brine (2×500 mL) and water (2×500 mL)
7. concentrationconcentrated to about 2 volumes
8. additionTo the mixture, was added t-butyl methyl ether (or MTBE, 300 mL)
9. temperatureThe mixture was heated at about 70° C. for 15 minutes
10. temperaturecooled to about 53° C. over one hour
11. customsimply re-crystallized) at 45° C.
12. customat 20-25° C.
13. customwith a glass pipette overnight
14. filtrationThe resulting solid was filtered via a medium pore-sized funnel
15. washwashed with a pre-cooled 10° C.
16. additionmixed solvent of heptane/MTBE (1/2 vol/vol) and suction
17. customdried in hood overnight

ORD record

ord-c6a94d361e384908bfa686ac08b91d45

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492395B2