反应详情

To 1.0 g of the crude product of 5-methyl-2-nitrobenzoic acid methyl ester synthesized in the foregoing step 1, there were added 1.4 g of N-bromosuccinimide, 0.5 g of benzoyl peroxide and 30 mL of benzene, the resulting mixture was refluxed with stirring for 4 hours and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 30 mL of acetonitrile, this solution was added to 36 mL of a 2M methylamine solution in THF and the mixture was further stirred at room temperature for 10 minutes. The solvent was distilled off under reduced pressure, then ethyl acetate was added, followed by the washing thereof four times with a 1M hydrochloric acid solution. The resulting ethyl acetate phase was washed with a saturated sodium hydrogen carbonate aqueous solution and a saturated common salt solution and the solvent was distilled off under reduced pressure. The crude product thus prepared was dissolved in 30 mL of acetonitrile, 1.1 g of di-tert-butyl-dicarbonate and 1.1 mL of triethylamine were added to the solution and the resulting mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, ethyl acetate was added thereto, the insoluble matter was then removed through filtration and the filtrate thus obtained was concentrated under reduced pressure. The resulting crude product was purified by the silica gel chromatography (hexane:ethyl acetate=90:10→80:20) to thus give 0.71 g of the title compound. MS (ESI+): m/z 325 (MH+).

1. temperaturethe resulting mixture was refluxed
2. distillationthe solvent was distilled off under reduced pressure
3. dissolutionThe resulting residue was dissolved in 30 mL of acetonitrile
4. additionthis solution was added to 36 mL of a 2M methylamine solution in THF
5. stirringthe mixture was further stirred at room temperature for 10 minutes
6. distillationThe solvent was distilled off under reduced pressure
7. additionethyl acetate was added
8. washThe resulting ethyl acetate phase was washed with a saturated sodium hydrogen carbonate aqueous solution
9. distillationa saturated common salt solution and the solvent was distilled off under reduced pressure
10. customThe crude product thus prepared
11. stirringthe resulting mixture was stirred at room temperature overnight
12. distillationThe solvent was distilled off under reduced pressure, ethyl acetate
13. additionwas added
14. customthe insoluble matter was then removed through filtration
15. customthe filtrate thus obtained
16. concentrationwas concentrated under reduced pressure
17. customThe resulting crude product was purified by the silica gel chromatography (hexane:ethyl acetate=90:10→80:20) to thus give 0.71 g of the title compound