合成路线1

1) Synthesis of Butanol (I): 1a) The reduction of 4,4,4-trifluoro-2-oxobutyric acid ethyl ester (III) with NaBH4 in dichloromethane gives 4,4,4-trifluoro-2-hydroxybutyric acid ethyl ester (IV), which is hydrolyzed with NaOH in ethanol, yielding the corresponding acid (V). The optical resolution of (V) with 1(S)-phenylethylamine in hot ethanol affords the 3(R)-hydroxy enantiomer (VI) (1,3), which is reduced with NaBH4 and BF3 ethearate in THF to provide 4,4,4-trifluorobutane-1,3(R)-diol (VII). Finally, this compound is monotosylated by means of tosyl chloride and DMAP in pyridine to afford intermediate (I). 1b) The digestion of 4,4,4-trifluoro-3-hydroxybutyric acid ethyl ester (IV) with Novozym in a phosphate buffer gives the corresponding (R)-enantiomer (VIII), which is reduced with NaBH4 in ethanol, yielding 4,4,4-trifluorobutane-1,3(R)-diol (VII) (4). Finally, this compound is monotosylated by means of tosyl chloride as before to give butanol (I).