Benzylamine → tert-Butyl 1-[3-(benzylamino)-4-fluorobenzyl]cyclopropanecarboxylate

Participants

Reaction Conditions

Reaction Steps

Under argon and dry conditions, 174.0 g (528.5 mmol) of tert-butyl 1-(3-bromo-4-fluorobenzyl)cyclopropanecarboxylate, 69.2 ml (634.2 mmol) of benzylamine, 4.84 g (5.29 mmol) of tris(dibenzylideneacetone)dipalladium, 60.95 g (634.2 mmol) of sodium tert-butoxide and 3.29 g (5.29 mmol) of (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were suspended in 1218 ml of toluene. The reaction mixture was then stirred at 110° C. for 2.0 h. After cooling, 2.1 liters of ethyl acetate and 1.7 liters of semisaturated aqueous ammonium chloride solution were added to the reaction mixture. After phase separation, the organic phase was washed with saturated ammonium chloride solution and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on 3.7 kg of silica gel (mobile phase petroleum ether/ethyl acetate 20:1). This gave 145.0 g (68.7% of theory) of the title compound.

Provenance & Evidence