N-(4-Methoxy-2-Methyl-5-nitrophenyl)acetaMide synthesis

Yield:196194-97-5 89%

Reaction Conditions:

with trifluoroacetic acid;sodium nitrite at 0 - 20;Inert atmosphere;

Steps:

4.3. N-(4-Methoxy-2-methyl-5-nitrophenyl)acetamide (2)

Based on a literature procedure,¹⁴ sodium nitrite (73 mg, 1.06 mmol) was added portion-wise to a stirred solution of 1 (189 mg, 1.06 mmol) in trifluoroacetic acid (5.0 mL) at 0 °C. The cooling bath was removed and the mixture stirred for 1 h before concentration in vacuo. The residue was dissolved in dichloromethane (10 mL), partitioned with sodium hydrogencarbonate (10 mL) and extracted with dichloromethane (3×10 mL). The organic layers were combined, dried (magnesium sulfate), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (SiO₂; 19:1 dichloromethane/methanol) affording the title compound2 (211 mg, 0.94 mmol, 89%) as an off-white solid: mp 185; δ_H (250 MHz, CD₃OD) 7.89 (1H, s, Ar-H), 7.15 (1H, s, Ar-H), 3.94 (3H, s, OCH₃), 2.32 (3H, s, CH₃), 2.16 (3H, s, CH₃); δ_C (125 MHz, CD₃OD) 171.5, 151.2, 141.3, 137.4, 128.6, 123.0, 115.5, 56.2, 21.9, 17.5; IR (neat) ν_max 1646, 1621, 1519, 1461, 1338, 1261, 1212, 1065, 1015, 760, 721; HRMS (ESI) found 247.0689, C₁₀H₁₂N₂NaO₄ [M+Na]⁺ requires 247.0689.

References:

Thompson, Sam;Vallinayagam, Ramakrishnan;Adler, Marc J.;Scott, Richard T.W.;Hamilton, Andrew D. [Tetrahedron,2012,vol. 68,# 23,p. 4501 - 4505] Location in patent:experimental part