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

Chapter 8 160mixture as solid in small portions. The reaction was completed after thelast addition. The mixture was diluted with water, and the product wasextracted with CHCl 3 , the organic phase was washed with (50ml) 1N HCl,saturated NaHCO 3 , saturated NaCl and the organic phase finally driedusing anhydrous Na 2 SO 4 . The organic phase was evaporated on arotavapor, the resulting crude solid was triturated with n-hexane. Thealcohol (±)-27c (14.6 mmoles, 95% yield) was recovered as white solid.Identical procedures were used for the syntheses of 27a-m; see table3.3, chapter 3 for chemical yields and reaction temperatures.8.4 Synthesis of (R)-(-)-2-(isoindonylinyl)-butane-1-ol (R)-(-)-24R-2-amino-1-butanole (0.84 mole; 79,64 ml) and 1,2-dichloroxylene(0.84 mole; 465.1 g) were added to a suspension of K 2 CO 3 (3.36 mol) in1 L of acetonitrile. The mixture was stirred using a mechanical stirrerunder reflux for 24h. The mixture was cooled to room temperature andthe K 2 CO 3 was filtered off. The solvent was evaporated and the resultingcrude oil was dissolved in EtOAc (750 ml). The organic solution waswashed with saturated NaHCO 3 (2 x 200 ml) , then the product wasextracted with 2N HCl solution (400 ml). 3N NaOH solution was added tothe acid solution until pH 12 was reached. The product was extracted withEtOAc (800 ml) and after solvent evaporation the crude product waspurified by two high vacuum distillations. 134 g (84% yield) of product(R)-(-)-24 were recovered.8.5 Synthesis of chiral alcohols 27a-d,g,i by asymmetricreduction:8.5.1.General synthetic procedure:To a 1 M solution of LiAlH 4 in Et 2 O (30 ml, 30 mmol) a solution of(R)-(-)-2-(2-isoindolinyl)butan-1-ol (R)-(-)-24 (14.32 g, 75 mmol) in200 ml of Et 2 O was added dropwise over 3 h at room temperature. After