Ethyl bromoacetate → {4-[(E)-3-(3-Chloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-acetic acid ethyl ester

Beteiligte Stoffe

Reaktionsschritte

A solution of 4.33 g (15.53 mmol) of 1-[(E)-3-(3-chloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 3A) in 80 ml of DMF was treated at 0° C. with 0.75 g (17.09 mmol) of NaH (55% in oil) in two portions and after 30 min with 1.89 ml (17.09 mmol) of bromo-acetic acid ethyl ester in 1 ml of DMF. The reaction was stirred for 5 h at RT, cooled (0° C.) and treated again with 0.20 g (4.66 mmol) of NaH (55% in oil) and after 20 min with 0.34 ml (3.11 mmol) of bromo-acetic acid ethyl ester. The reaction was warmed up to RT over night, cooled and neutralized with cold aqueous 10% KHSO4 and extracted with Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (EtOAc/n-heptane 1:1 to 9:1) to yield 2.92 g (52%) of the title compound as light yellow viscous oil. MS: 365.0 (MH+, Cl).

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