Development and validation of HPLC method for the resolution of derivatives of 1-bromo-3-chloro-2-propanol: a novel chiral building block for the synthesis of pharmaceutically important compounds

Abstract

The methods for the separation of racemic compounds [(RS)-1-bromo-3-chloro-2-propanol, (RS)-1-bromo-3-chloropropan-2-yl acetate] into the corresponding enantiomers were tried to develop in high performance liquid chromatography in a single injection mode. In the case of HPLC, both the reversed (Phenomenex Lux 5u cellulose-1, Lux 5u cellulose-2, Lux 5u amylose-1) and normal phase (Chiralcel OJH, ODH, ADH) chiral columns were used for this purpose. HPLC methods could not resolute the desired enantiomers. However, phenoxy derivatives of (RS)-1-bromo-3-chloro-2-propanol and (RS)-1-bromo-3-chloro- propan-2-yl acetate were separated by normal phase (ODH) column using a mobile phase consisting of n-hexane and isopropanol (80: 20) at a flow rate of 0.5 mL/min (25°C) and detected at 254 nm. The method was validated for linearity, range, accuracy and precision. The developed method was applied for monitoring the progress of lipase catalyzed enantioselective synthesis of (S)-1-bromo-3-chloropropan-2-yl acetate from (RS)-1-bromo-3-chloro-2-propanol. All the analytes were synthesized chemically.