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

Chapter 8 1638.9 Decarboxylation of the diacids 34 to 1-Alkylimidazoles 35and Bifonazole 6a.8.9.1 Decarboxylation: general procedure.A solution of 34 (10 mmol) in 20 ml of diphenyl ether was heated atreflux for 0.5 h and, after cooling, applied to a silica gel column. Elutionwith Et 2 O eliminated the excess diphenyl ether and further elution withAcOEt led to the products, which were further purified by preparativeTLC (AcOEt for 35a and 35b, CHCl 3 /MeOH 98:2 for 35c) orrecrystallization (for 35d and 6a). For yields, absolute configurations andoptical purities (% ee) of the products, see Table 4.4, chapter 4.8.10 Synthesis of 4-(5)-ethyl imidazole carboxylate 37:8.10.1 Synthesis of acetylglycine ethyl ester 38:To a suspension of acetyl glycine hydrochloride(100 mmol) indichloromethane (400 ml) at 0° C triethylamine (TEA; 220 mmol) andacetyl chloride (100 mmol) were added. After two hours the reactionmixture was diluted with dichloromethane and water, the organic phasewas separated and washed with 1 N HCl solution, saturated NaCl solution,and then dried over anhydrous Na 2 SO 4 . The solid 38 was recovered afterevaporation (98 mmol, 98 % yield).8.10.2 Synthesis of ethyl 4(5)-(2-thiol)-imidazole carboxylate40:Sodium methoxide (95 mmol) was added to a solution of acetylglycine ethyl ester 38 (86 mmol) in benzene at 0°C in 10 small solidportions. Ethyl formiate (258 mmol) was then added dropwise. Thereaction was carried out for 24 h at 0°C. An orange solid precipitated inthe reaction mixture and cold water (55ml) was added to the mixturewhich then became clear. The benzene solution was separated from the