Hydrochloric Acid → 2-Bromo-5-chloro-4-methyl-benzoic acid methyl ester

HRID 1716954Notes

Reaction equation

N[C:2]1[C:3]([CH3:13])=[CH:4][C:5]([Br:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[ClH:14].N([O-])=O.[Na+]>O1CCOCC1.O.[Cu]Cl>[Br:12][C:5]1[CH:4]=[C:3]([CH3:13])[C:2]([Cl:14])=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]

Participants

Conditions

Temperature: 5 °C

Procedure

To a cooled solution (15° C.) of methyl 5-amino-2-bromo-4-methylbenzoate (122 g, 0.5 mol) in 1,4-dioxane (633 mL), was added conc. hydrochloric acid (550 mL). After the mixture was cooled to 5° C., a solution of sodium nitrite (35.53 g, 0.515 mol) in 83 mL of H2O was added dropwise at such a rate that the reaction temperature was kept below 0° C. After being stirred at 0° C. for 2 hours, the reaction mixture was added slowly to a flask containing copper (I) chloride (59.4 g, 0.6 mol) and conc. hydrochloric acid (275 mL). It was stirred for 40 min, at which time TLC demonstrated that the reaction was complete. The reaction mixture was poured over ice water (2 L) and then filtered. The filter cake was dissolved in ethyl acetate (1.5 L). The organic layer was washed with brine (3×500 mL), dried over anhydrous Na2SO4. Concentration under reduced pressure provided the title compound as light yellow crystals. Yield: 120 g (92.6%). 1H NMR (CDCl3, 300 MHz): δ 7.82 (s, 1H), 7.54 (s, 1H), 3.92 (s, 3H), 2.38 (s, 3H); MS ESI (m/z) 262 (M)+, calc. 262.

Workup

customwas kept below 0° C
additionthe reaction mixture was added slowly to a flask
stirringIt was stirred for 40 min, at which time TLC
filtrationfiltered
dissolutionThe filter cake was dissolved in ethyl acetate (1.5 L)
washThe organic layer was washed with brine (3×500 mL)
dry with materialdried over anhydrous Na2SO4
concentrationConcentration under reduced pressure

Sources & evidence

ORD record: ord-0ef43440a50b4235bb9d017bd976622c
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07803778B2

Reaction notes

Loading…