Preparing aminoepoxides by reacting aminoaldehyde with a halomethyl organometallic reagent and solvent

摘要

A method of preparing an aminoepoxide, wherein a protected aminoaldehyde is reacted with a halomethyl organometallic reagent in an appropriate solvent at a temperature above -80 °C. The halomethyl organometallic reagent is formed by a reaction between an organometallic reagent and a dihalomethane and the improvement comprises 1) flowing the protected aminoaldehyde into a mixing zone maintained at a temperature below 0 °C, and 2) flowing the halomethyl organometallic reagent in the mixing zone for contacting in the mixing zone with the protected aminoaldehyde, 3) withdrawing from the mixing zone reaction products of the protected aminoaldehyde and the halomethyl organometallic reagent. The obtained aminoepoxides are useful, through amine opening of the epoxide ring, as intermediates in the preparation of pharmaceuticals, e.g. HIV protease inhibitors.