3-(5-METHYL-1,2,4-OXADIAZOL-3-YL)ANILINE synthesis

Yield:-

Reaction Conditions:

Stage #1: 3-amino-N-hydroxybenzenecarboximidamidewith sodium hydride in tetrahydrofuran at 65; for 0.5 h;Molecular sieves;
Stage #2: acetic acid methyl ester in tetrahydrofuran at 20;Heating / reflux;

Steps:

To a stirred solution of Intermediate 18 (5. 3g) in dry tetrahydrofuran (50ML) was added 4A molecular sieves, followed by sodium hydride (60% dispersion in mineral oil ; 1. 5g) and the mixture heated at 65°C for 30 min. After cooling to room temperature methyl acetate (2. 8MOI) was added and the mixture heated under reflux for 16h. After cooling to 20°C the mixture was added to water (100ML) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulphate and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with DICHLOROMETHANE to give the title compound as a white solid (4. 0G). TLC SI02 (30% ethyl acetate in cyclohexane) Rf = 0. 22

References:

WO2004/103998,2004,A1 Location in patent:Page 76-77