An Improved Method of Manufacturing Methyl Morphine (Codeine) and Ethyl Morphine.
Year: 1898

page_text: Date of Application, 22nd Aug., 1898
Complete Specification Left, 20th May, 1899-Accepted, 22nd July, 1899
PROVISIONAL SPECIFICATION.
An Improved Method of Manufacturing Methyl Morphine (Codeine)
and Ethyl Morphine.
I, ERNST KAUDER, of 76, Beckstrasse, Darmstadt, in the Empire of Germany,
Doctor of Philosophy, Chemist, do hereby declare the nature of this invention
to be as follows:-
The methods of manufacturing alkyl ether of morphine, methyl ether (codeine)
or ethyl ether (codethyline) as at present known, have the disadvantage that they-
only yield a small amount of the desired ethers.
When treating morphine with methyl iodide or ethyl iodide (see Grimaux,
Annales Chim. 75/27, 274 and 278, and Hesse Annalen der Chem. und Pharm.
222 page 210), such small quantities are obtained, that this method appears from
a technical point of view to be of no importance.
But even in the action of sodium methylate and sodium ethylate the same
disadvantage is experienced inasmuch as a large portion of the morphine escapes
reaction and only admits of being partly rendered re-utilizable by repeating
the operation after its recovery which cannot be effected without loss.
In view of the fact, that one alkyl group, of the neutral sulphuric acid esters
is split off with great facility, these esters have been practically employed for
producing morphine esters.
It has now been found that the neutral sulphuric acid esters may be advan-
tageously substituted by esters of phosphoric acid, it being preferable in this
operation, to heat the mixture up to a temperature varying between 80 and 100
degrees Centigrade.
EXAMPLE:
100 parts of morphine are dissolved with 800 parts of alcohol (methyl, ethyl,
or the like) and with 13.2 parts of hydrate of soda (or alcoholate) to which mix-
ture 46.2 parts of trimethylphosphate are added.
This mixture is then heated for some hours, up to a temperature varying
between 80 and 100 degrees Centigrade, in a closed or open vessel, provided with
a refrigerator. The separation of the codeine and also of the morphine, if the
latter is desired to be recovered, is effected according to known methods.
Dated this 22nd day of August 1898.
45, Southampton Buildings, London, W.C., Agents for the Applicant.
COMPLETE SPECIFICATION.
An Improved Method of Manufacturing Methyl Morphine (Codeine)
and Ethyl Morphine..
I, ERNST KAUDER, of 76, Beckstrasse, Darmstadt, in the Empire of Germany,
Doctor of Philosophy, Chemist, do hereby declare the nature of this invention
[Price Sd1

page_text: and in what manner, the same is to be performed, to be particularly described and
ascertained in and by the following statement:-
The methods of manufacturing alkyl ether, of morphine, methyl ether (codeine)
or ethyl ether (codethyline) as at present known, have the disadvantage that they
only yield a small amount of the desired ethers.
When treating morphine with methyl iodide or ethyl iodide (see Grimaux,
'Annales Chim. /5/27, 274 and 278, and Hesse Annalen der Chem. und Pharm.
222 page 210), such small quantities are obtained. that this method appears from
a technical point of view to be of no importance.
But even in the action of sodium methylate and sodium ethylate, the same
disadvantage is experienced inasmuch as a large portion of the morphine escapes
reaction and only admits of being partly rendered re-utilizable by repeating
the operation after its recovery which cannot be effected without loss.
In view of the fact; that one alkyl group of the neutral sulphuric acid esters
is split off with great facility, these esters have been practically employed for
producing morphine esters from morphine alkalis or morphine alkaline earths
in suitable solvents. The neutral sulphuric acid esters have been formerly
employed as follows: To a solution of morphine (practically in an alcohol such
as methylic or ethylic alcohol) mixed with somewhat more than the predetermined
quantity of alkali (in the form of hydrate or alcoholate) or alkaline earths, is
added the neutral sulphuric ester, the quantity preferably exceeding one mole-
cule. The reaction commences at once in a cold condition and is accelerated and
terminated by warming on the water bath.
It has now been found that the neutral sulphuric acid esters may be advan-
tageously substituted by esters of phosphoric acid, it being preferable in this
operation, to heat the mixture up to a temperature varying between 80 and 100
degrees Centigrade.
EXAMPLE:
100 parts of morphine are dissolved with 800 parts of alcohol (methyl, ethyl,
or the like) and with 13.2 parts of hydrate of soda (or alcoholate) to which mix-
ture 46.2 parts of trimethylphosphate are added.
This mixture is then heated for some hours, up to a temperature varying
between 80 and 100 degrees Centigrade, in a closed or open vessel, provided with
a refrigerator. The separation of the codeine and also of the morphine, if the
latter is desired to be recovered, is effected according to known methods.
Having now particularly described and ascertained the nature of my said in-
vention and in what manner the same is to be performed, I declare that what I
claim is:-
A process for the production of methyl-morphine (codeine) or ethyl-morphine
by means of the action of phosphate of methyl or ethyl upon morphine alkali
or morphine alkaline earths in suitable solvents.
Dated 1: 0041 Ja of 1900
HASELTINE, LAKE & Co.,
45, Southampton Buildings, London, W.C.,
Agents for the Applicant.