Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 8 1668.14 Synthesis of 5-amino-1-(2-octyl)imidazole-4-carboxylicacid (±)-47:A mixture of 5-amino-1-(2-octyl)imidazole-4-carbonitrile 46 (0.30g, 1.36 mmol), EtOH (3 ml) and aqueous 10 N NaOH (3 ml) was heatedunder reflux for 24 h. The solution was cooled to room temperature,diluted with water (2 ml) and neutralized by slow addition of 2 N HCl.After 2 h in a cool place, the precipitate was filtered off and washed withwater to give 5-amino-1-(2-octyl)imidazole-4-carboxylic acid (47) (0.32g, 115%) as a chromatographically pure (5% AcOH in AcOEt, Rf 0.58),white crystalline solid with no defined melting point, containing somecrystal water.8.15 Synthesis of 5-amino-1-(2-octyl)imidazole 48The 5-amino-1-(2-octyl)imidazole-4-carboxylic acid 47 wasdecarboxylated following the same procedure 7.9 as described for acids34 affording 5-amino-1-(2-octyl)imidazole 48 in 15% yield.8.16 Synthesis of 1-(2-Octyl)imidazole-4-carboxamide 49:A solution of 5-amino-1-(2-octyl)imidazole-4-carbonitrile 46 (0.33g, 1.5 mmol) in 10 ml of THF was added during 1 h to a refluxingsolution of isoamyl nitrite (0.63 ml, 4.5 mmol) in 5 ml of THF. Afterbeing heated under reflux for 1 h, the reaction mixture was cooled,concentrated and purified by flash chromatography (2.5% Et 3 N inAcOEt, Rf 0.45) to provide 49 (0.19 g, 45%) as a white amorphouspowder with no defined melting point.8.17 General procedure for the synthesis of N-[2,2-(Dimethoxy)ethyl]amines 52a and 52b.To a solution of (S)-(+)-2-octylamine (+)-44 and (S)-(-)-_-methylbenzylamine (-)-51 (4.0 mmol) in 30 ml of CH 3 CN were addedanhydrous K 2 CO 3 (0.83 g, 6.0 mmol) and bromoacetaldehyde dimethylacetal (0.68 g, 4.0 mmol). The reaction mixture was heated under reflux