Sodium Iodide → ethyl [(4-methoxyphenyl)amino]acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of sodium iodide (122 g, 0.81 mol) and sodium acetate trihydrate (221 g, 1.62 mol) in water (200 mL) was added 4-methoxyaniline (3) (100 g, 0.81 mol) followed by ethyl 2-bromoacetate (90 mL, 812 mmol) the reaction was stirred at 90° C. for 3 h. The reaction mixture was cooled to RT and partitioned with EtOAc (1 L), the organic phase was separated, washed with water (400 mL), 1 M HCl (aq.) (3×500 mL), and the organic phase discarded. The combined acidic extracts were cooled to 0° C. and solid NaOH was added to pH 14 and the aqueous phase was extracted with EtOAc (3×400 mL). The combined organics were washed with brine (250 mL), dried (MgSO4), filtered and solvents removed in vacuo to give ethyl 2-((4-methoxyphenyl)amino)acetate (17) (128 g, 75%) as a purple oil that crystallised on standing: m/z 210 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 6.75-6.69 (m, 2H), 6.55-6.46 (m, 2H), 3.99 (t, J=6.5 Hz, 1H), 4.10 (q, J=7.1 Hz, 2H), 3.82 (d, J=6.5 Hz, 2H), 3.63 (s, 3H), 1.19 (t, J=7.1 Hz, 3H).

Provenance & Evidence