We Claim
1. An improved process for the preparation of |-Ephedrine &d-Ephedrine from dl-
Ephedrine which comprises
(i).dissolving dl-Ephedrine base in an organic solvent as mentioned here under,
(ii) adding an achiral acid as mentioned here under, to the resulting solution and stirring
the solution for a period ranging from 5 min to 3hrs
(iii) adding a solution of an ester of tartaric acid in an organic solvent to the solution
obtained in step (ii) at a temperature in the range from -10°C to 70°C for a period
ranging from $ min to Shrs
(iv) stirring the resulting solution for a period ranging from 10min to 10 hr
(v) adding a polar solvent to the resulting solution in step (iv) and cooling to a
temperature in the range of -10°C to 40°C to obtain a slurry containing solid mass of d-
Ephedrine tartaric acid ester complex
(vi) maintaining the resulting slurry for a period ranging from 1Smin to 10 hr and
filtering to obtain a mother liquor separating d-ephedrine
(vii) adding to the mother liquor, concentrated or dil hydrochloric acid and concentrating
the mother liquor ,
(viii) adding water or solvents to the concentrated mother liquor
(ix) cooling the concentrated mother liquor to a temperature in the range of -15°C to
40°C and filtering to get !-Ephedrine hydrochloride,(%) adding organic solvent along with organic or inorganic acids to the d-Ephedrine ~
tartaric acid ester complex contained in the residue in step ( vi) and removing water
present in the acid used by known methods
(xi) adding an organic solvent to the concentrated mass obtained in step ( x) under
stirring for a period ranging from 10min to 10hr and filtering, the d-Ephedrine
hydrochloride remaining as the residue and the mother liquor containing the resolving
agent and
(xii) concentrating the mother liquor obtained in step (xi) and basifying and acidifying
by conventional methods and filtering the resolving agent
2. The improved process as claimed in claim! wherein the Ephedrine base used in step-
(i) is selected from derivatives of 2-amino -1-phenyl propanol
3. The improved process as claimed in claims 1 to 2 wherein the organic solvent used in
step (1) is selected from organic solvents or water, preferred is methanol.
4.The improved process as claimed in claims | to 3. wherein the achiral acid used in step
~(ii)is acetic acid
5. The improved process as claimed in claims | to 4 wherein the tartaric acid ester used
in step-(iii) is selected from dibenzoy! tartaric acid and ditoluoyl tartaric acid, preferably
dibenzoyl tartaric acid
6. The improved process as claimed in claims | to S wherein the amount of ester used is
0.2 to 1.0 eq to that of the base used , preferably 0.25eq
7. The improved process as claimed in claims | to 6 wherein the solvent used to dissolve
the tartaric ester is methanol8. The improved process as claimed in claims 1 to 7 wherein the step ( iii) is effected at a
temp ranging from 30-35° C for a period ranging from a period 10min 1030 min
9. The improved process as claimed in claims 1 to 8 wherein the stirring the solution is
done in step (iv) for aperiod ranging 30 min to60min
10. The improved process as claimed in claims 1 to 9 wherein the polar solvents used in
step (v) is water and the amount used is in the range from 2to 10 times to the quantity of
base used preferably 3.5 times
11. The improved process as claimed in claims 1 to 10 wherein the cooling in step (v) is
effected in the range preferably 20° C to 40 deg C
12. The improved process as claimed in claims | to 11 wherein the mass obtained in step
(vi) is maintained for Ihr before filtering the Ephedrine — tartaric acid ester complex
13. The improved process as claimed in claims 1 to 12 wherein the mass is concentrated
in step(vii) after the addition of concentrated or dil hydrochloric acid
14, The improved process as claimed in claims | tol3 wherein the solvent used in step-
(viii) is selected from water, aliphatic ketones or alcohols , preferably acetone
15, The improved process as claimed in claims 1 to 14 wherein the mass is cooled in
step-(ix) to a temperature in the range of 10°C to 15°C before filtering the material
16. The improved process as claimed in claims 1 to 15 wherein the solvents used in
step-(x) is selected from aliphatic ketones or aromatic ketones or alcohols preferably
benzene or toluene
17. The improved process as claimed in claims 1 to 16 wherein the acid used in step (x)
is an organic or inorganic acid, preferably hydrochloric acid
1518TH¢. improved process as claimed in claims 1 to 17 wherein solvents like aliphatic
ketones or aromatic ketone or alcohols preferably acetone is added in step (xi)under
stirring for preferably 15 min to 30min
19Tke. improved process as claimed in claims 1 to 18 wherein the mother liquor of
step(xi) is concentrated and basified by adding water and acidified and filtered the
tartaric acid ester
20The improved process for the preparation of d-Ephedrine & I-Ephedrine from dl-
Ephedrine substantially as herein described with reference to the Example
Dated this 3rd day of MAY 2004 )
{
(V.NGOPALAKRISHNAN) (M.DEVESH)
EXECUTIVE DIRECTOR MANGING DIRECTOR
MALLADI DRUGS & EMMELLEN BIOTECH
PHARMACEUTICALS LTD PHARMACEUTICALS LTD