Triethylamine → Tert-butyl 3-(3-amino-2-methylphenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

Under argon, 201 ml (1.39 mol) of tert-butyl prop-2-enoate were added dropwise to a solution of 100 g (463 mmol) of 1-bromo-2-methyl-3-nitrobenzene, 322 ml (2.31 mol) of triethylamine, 28.18 g (92.58 mmol) of tri-2-tolylphosphine and 10.39 g (46.29 mmol) of palladium(II) acetate in 2 liters of DMF, and the mixture was then stirred at 125° C. for 36 h. After cooling to room temperature, the reaction mixture was stirred with saturated aqueous ammonium chloride solution and the organic phase was separated off. The aqueous phase was extracted three times with tert-butyl methyl ether, and the combined organic phases were washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration, the solvent was removed to dryness under reduced pressure. The residue obtained was purified by flash chromatography on silica gel (mobile phase petroleum ether/ethyl acetate 9:1). This gave 89 g (338 mmol, 73% of theory) of the intermediate tert-butyl(2E)-3-(2-methyl-3-nitrophenyl)prop-2-enoate as a colorless solid. 88 g (334 mmol) of this solid were dissolved in 2 liters of ethanol, 7 g of palladium on carbon (10%) were added at room temperature and the mixture was hydrogenated at atmosperic pressure for 18 h. After the reaction had gone to completion, the reaction solution was filtered through kieselguhr and the filtrate obtained was concentrated under reduced pressure. This gave 61.3 g (260.5 mmol, 78% of theory) of the title compound as a colorless solid.

Provenance & Evidence