Synthesis
GENERAL METHOD: To a tetrahydrofuran (THF, 10 mL) solution of Fmoc-L-leucine (10 mmol) was sequentially added N,N-diisopropylethylamine (DIPEA, 11 mmol, 1.42 mL) and 50% propylphosphonic anhydride (T3P) in ethyl acetate (EtOAc) solution (20 mmol, 6.36 mL) at 0 °C and the reaction mixture was stirred for about 10 min at this temperature. The reaction mixture was stirred for about 10 minutes. Subsequently, an aqueous solution of sodium borohydride (NaBH4, 10 mmol, 388 mg) (0.3 mL) was slowly added to the reaction system at the same temperature and the reaction was continuously stirred until the reaction was completed by thin layer chromatography (TLC). After completion of the reaction, the solvent was removed by rotary evaporator and the crude product was extracted with ethyl acetate (EtOAc). The organic phase was washed sequentially with 5% aqueous citric acid (10 mL × 2), 5% aqueous sodium carbonate (Na2CO3) (10 mL × 2), water and saturated saline. The organic layer was dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to obtain Fmoc-L-leucinol.
References
[1] Journal of Organic Chemistry, 2001, vol. 66, # 25, p. 8454 - 8462
[2] Angewandte Chemie - International Edition, 2010, vol. 49, # 1, p. 117 - 120
[3] Organic and Biomolecular Chemistry, 2010, vol. 8, # 21, p. 4855 - 4860
[4] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5059 - 5063
[5] Organic Letters, 2008, vol. 10, # 10, p. 1881 - 1884
