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

Chapter 8 169room temperature for two hours. Methanol was evaporated , the resultingoil was dissolved in ethylacetate and washed with 0.5 N NaOH solution.The organic phase was washed with saturated solution NaCl and driedover anhydrous Na 2 SO 4 . The crude oil was purified by flashchromatography on silica gel.See chapter 4, table 4.8 for the chemical yields.8.22 Synthesis of diamides 57: general procedureDiacid (±)-34e (1.25 mmol) was dissolved in dry dioxane (20ml)containing carbonyl diimidazole (CDI; 2.89 mmol) and chiral amine (2.55mmol). The mixture was refluxed for 8 h and after cooling, the solventwas evaporated. The crude reaction mixture was dissolved in CHCl 3, andthe solution washed consecutively with 1N HCl, saturated NaHCO 3solution and saturated solution of NaCl. The crude product was purifiedby preparative TLC (eluent CH 2 Cl 2 -MeOH- AcOH 98:1:1). The twodiasteroisomers were completely separated in 1:1 ratio. Overall yield was90%.8.23 Synthesis of Aryl propynoles8.23.1 Synthesis of 1-phenyl-2-propyn-1-ol (±)-58a byaddition of lithium acetylide to benzaldeyde:Benzaldehyde (3.5 mmol) was dissolved in 10 ml of dry THF, thesolution was cooled to -78°C, and a 1N solution of lithium acetylide inTHF (3.7 mmol) was added dropwised over 30 min. After the addition thetemperature was raised to 0°C. The mixture was quenched with asaturated solution of NH 4 Cl and was diluted with CH 2 Cl 2 and water. Theorganic phase was separated and washed with a saturated solution of NaCl,and then dried over anhydrous Na 2 SO 4 . The product was purified byflash chromatography on silica gel. The 1-phenyl-2-propyn-1-ol (±)-58awas recovered as colorless oil in 45 %yield.Following the same procedure but with the addition of ethylendiamine to the benzaldehyde solution the yield of (±)-58a was 42%.