Process for the preparation of enantiomerically pure 3-phenyl-3-hydroxypropylamine

An improved process for the preparation of enantiomerically pure 3-phenyl-3-hydroxy propyl amine, said process comprising the steps of:

• i. adding osmium tetraoxide to a mixture of potassium ferricyanide, potassium carbonate, chiral ligand in an aqueous organic solvent at a temperature in the range of 0 to 5° C.;
• ii. stirring the mixture obtained in step (i) with styrene at a temperature in the range of 0 to 5° C. for 12 to 24 hours and then quenching with solid sodium sulfite;
• iii. further stirring the contents of step (ii) for a period range of 30 minutes to 2 hours and extracting with ethylacetate repeatedly;
• iv. washing the combined ethylacetate extracts with brine, drying over anhydrous Na2SO4, filtering and concentrating to obtain a crude product;
• v. purifying the crude product obtained in step (iv) over silica-gel column using a proportionate mixture of petroleum ether and ethyl acetate to obtain pure chiral diol compound of formula (2);
• vi. reacting chiral diol of formula (2) with an activating reagent portion wise in presence of a base stirring it for a period in the range of 15 to 24 hours at a temperature range of −40° C. to 35° C. and then quenching to obtain compound of formula (3);
• vii. reacting compound of formula (3) obtained from step (vi) with a metal cyanide in an aqueous alcohol at room temperature for a period of 15 to 24 hours, concentrating it at a temperature range of 40-70° C., extracting with brine, drying over anhydrous Na2SO4, purifying it over silica gel column to obtain a pure chiral cyano compound of formula (4);
• and
• viii. reducing the compound of formula (4) obtained from step (vii) with a reducing agent at −15 to 0° C., refluxing for a period of 1-3 hours, extracting the mixture with an organic solvent and then concentrating to obtain the product of formula (1).