Diisopropylamine → (+/-)-tert-Butyl 1-[(3-bromo-4-chlorophenyl)(hydroxy)methyl]cyclopropanecarboxylate

Participants

Reaction Conditions

Reaction Steps

42.2 ml (105.5 mmol) of a 2.5 M solution of n-butyllithium in hexane were added dropwise to a solution, cooled to from −20° C. to −30° C., of 14.8 ml (105.5 mmol) of diisopropylamine in 60 ml of abs. THF. After the addition had ended, the mixture was stirred at from −20° C. to −30° C. for another 30 min. The mixture was then cooled to −78° C., and a solution of 12.0 g (84.4 mmol) of tert-butyl cyclopropanecarboxylate in 60 ml of abs. THF was added dropwise at this temperature. After 4 h at −78° C., a solution of 15.4 g (70.3 mmol) of 3-bromo-4-chlorobenzaldehyde in 60 ml of abs. THF was added. The reaction mixture was slowly warmed to RT overnight, saturated aqueous ammonium chloride solution was then added and the mixture was extracted with ethyl acetate. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1→10:1). This gave 16.2 g of the target compound (52.5% of theory).

Provenance & Evidence