Benzyl Bromide → methyl N-benzyl-N-(3-chloro-4-fluorophenyl)alaninate

Participants

Reaction Conditions

Reaction Steps

Methyl N-(3-chloro-4-fluorophenyl)alaninate (1-3, 0.740 g, 3.194 mmol) was treated with benzyl bromide (0.955 mL, 7.986 mmol) and tertbutylammonium iodide (0.118 g, 0.319 mmol) at 25° C. in DMF (100 mL) then allowed to stir 15 min. NaH was added (0.100 g, 4.153 mmol) and the resulting suspension was warmed at 50° C. while stirring over 48 h. Upon completion, the reaction was diluted with EtOAc (100 mL) and washed with NaHCO3 (sat. aq) (3×75 mL). The organic fractions were dried over sodium Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash column chromotography (SiO2, 0-40% EtOAc/hexanes gradient) to give methyl N-benzyl-N-(3-chloro-4-fluorophenyl)alaninate (2-1). 1H NMR (300 MHz, CDCl3) δ 7.31 (m, 5H), 6.91 (t, J=8.8 Hz, 1H), 6.73 (m, 1H), 6.49 (m, 1H), 4.47 (m, 3H), 3.73 (s, 3H), 1.22 (d, J=6.0 Hz, 3H). MS 322.3 found, 322.8 (M+H+) required.

Provenance & Evidence