2-Methoxy-5-nitroaniline → Acetamide, N-(2-methoxy-5-nitrophenyl)-

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Reaction Steps

2-Methoxy-5-nitroaniline 23 (13.17 gm, 0.078 moles) was dissolved in 60 ml tetrahydrofuran (THF) at room temperature under argon. Acetic anhydride (11.1 ml, 0.118 moles) was added. An orange solution was formed. The mixture was evaporated under reduced pressure, and kept under vacuum overnight to give N-(2-Methoxy-5-nitrophenyl)acetamide 24 (1H NMR (CDCl3) δ 9.20, 1H, br s; 7.99, 1H, d; 6.95, 1H, d; 4.02, 3H, s; 3.12, 1H, s; 2.26, 3H, s), which was suspended in 115 ml ethanol. 5% Palladium on carbon (8.05 gm) was added, followed by the slow addition of 8.05 ml hydrazine hydrate (1 ml/5 minutes). After 90 minutes of heating, TLC indicated the reduction was complete. The mixture was filtered and the cake was washed with six 100 ml portions of methanol. The combined filtrate was concentrated under reduced pressure, taken up in 100 ml methanol and filtered again through Celite. The filtrate was concentrated to an oil and triturated with DCM and methanol to give crystals of N-(3-amino-6-methoxyphenyl)acetamide 25 (12.8 gm, 91% from 23) in two crops. 1H NMR (CDCl3) δ 7.85, 1H, m; 7.80, 1H, br s; 6.67, 1H, d; 6.37, 1H, dd; 3.79, 3H, s; 3.5, 2H, br; 2.17, 3H, s.

Provenance & Evidence