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.

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. [ABSTRACT FROM AUTHOR]