5-methoxy-4-methyl-2-nitrobenzonitrile synthesis

Yield:959137-56-5 57%

Reaction Conditions:

Stage #1: 2-nitro-4-methyl-5-methoxy anilinewith sulfuric acid;sodium nitrite in water at 0; for 0.833333 h;
Stage #2: copper(I) cyanide in water;Heating / reflux;

Steps:

46.a

A solution of 5-methoxy-4-methyl-2-nitroaniline (1Og, 55mmol) in concentrated H₂SO₄ (12mL) was added slowly to vigorously stirred H₂O maintained below 5⁰C. To the resultant orange suspension a solution of sodium nitrite (3.93g, 57mmol) in H₂O (4OmL) was added drop- wise, and the mixture was stirred at O⁰C for 50min. The solution obtained was then added in portions to a hot solution of CuCN (freshly prepared from CuSO₄ (34.4g) and KCN (36.3g) in H₂O (16OmL). Once addition was complete the warm reaction mixture was filtered. The isolated solid obtained was washed with H₂O and allowed to dry. The solid was repeatedly washed with CHCl₃ and the washings decanted. The combined washings were evaporated to dryness and the residue chromatographed (DCM-hexanes (3:1)) to afford the product (6.Og, 57%). ¹B NMR (CDCl₃) 8.14 (IH, s), 7.19 (IH, s), 4.00 (3H, s), 2.36 (3H, s).

References:

WO2007/135417,2007,A1 Location in patent:Page/Page column 82