Practical Oxirane Ring Opening with In Situ Prepared LiCN; Synthesis of (2S,3R)-3-(2,4-Difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)-1-butanenitrile

Abstract

Trisubstituted oxirane 1 was regiospecifically opened with LiCN in situ prepared from acetone cyanohydrin and LiH to provide the corresponding β-hydroxy nitrile 2 in satisfactory yield, enabling us to manufacture a key intermediate for a new antifungal agent on a multi-kg scale. Some applications of this method to the ring opening of other oxiranes and nucleophilic substitution are also described.

Notes

¹H-NMR (CDCl₃) δ: 1.28 (3H, d, J, = 6 Hz), 3.68 (1H, d, J, = 6 Hz), 4.13—-4.22 (1H, m), 4.90 (1H, d, J, = 5 Hz), 5.19 (1H, d, J, = 5 Hz), 6.82—-6.91 (2H, m), 7.68—-7.76 (1H, m), 7.87 (1H, s), 8.15 (1H, s).; Mass: 288 [MH]⁺.