A Process for the Production of Methyl-morphine (Codeine) and Ethylmorphine.
Year: 1898

page_text: Date of Application, 30th June, 1898
Complete Specification Left 14th Feb. 1800 Accented 15th An
1800
PROVISIONAL SPECIFICATION.
A Process for the Production of Methyl-morphine (Codeine) and
Ethylmorphine.
I, Dr. ALEXANDER EHRENBERG, of 45, Hochstrasse, Darmstadt, Grand Duchy of
Hessen, in the Empire of Germany, Chemist, do hereby declare the nature of this
invention to be as follows:-
The methods hitherto employed for the production of the alkylether of mor-
phine and of methylether (codeine) or ethylether (codethyline) are defective
inasmuch as they yield but a small quantity of the desired ether. By the treat-
ment of morphine with methyliodide or ethyliodide (compare Grimaux, Chemical
Records (5) 27, 274 and 278, Hesse, Records of Chemistry and Pharmacy 222
page 210) such small quantities were obtained that this method appears to possess
no importance from a technical point of view. By the action of sodium methy-
late and sodium ethylate (English Patent No. 10281 of 1886) this defect is
rendered evident owing to the fact that a large portion of the morphine of the
reaction is abstracted and can only be again rendered partially serviceable after
its recovery, which cannot be effected without loss, by means of a repetition of
the operation.
Owing to the fact that one alkyl group, the neutral sulphuric acid ester, may
be very readily split up, these esters are specially adapted for the production of
morphine esters.
The process is as follows: To an alcoholic solution of morphine 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 acid ester, the
quantity in excess being preferably one molecule. The reaction commences at once
in a cold condition and is accelerated and terminated in the water bath.
The isolation of the codeine and small quantities of morphine, which have been
almost abstracted by the reaction, is affected by the known methods.
Example:
1 kilogramme of morphine,
85 grammes of metallic sodium,

page_text: A Process for the Production of Methyl-morphine (Codeine) and
Ethylmorphine.
I, Dr. ALEXANDER EHRENBERG, of 45, Hochstrasse, Darmstadt, Grand Duchy of
Hessen, in the Empire of Germany, Chemist, do hereby declare the nature of this
invention and in what manner the same is to be performed, to be particularly
described and ascertained in and by the following statement:-
The methods hitherto employed for the production of the alkylether of mor-
phine and of methylether (codeine) or ethylether (codethyline) are defective
inasmuch as they yield but a small quantity of the desired ether. By the treat-
ment of morphine with methyliodide or ethyliodide (compare Grimaux, Annales
de Chimie (5) 27, 274 and 278, Hesse, Annalen der Chemie und Pharmacie 222
page 210) such small quantities were obtained that this method appears to possess
no importance from a technical point of view. By the action of sodium methy-
late and sodium ethylate (English Patent No. 10281 of 1886) this defect is
evident from the fact that a large portion of the morphine does not participate
in the reaction, and this can only in part be rendered serviceable after its recovery,
by repeating the operation, which however cannot be effected without loss.
Owing to the fact that the one alkyl group of the neutral sulphuric acid ester may
be readily separated, these esters are specially adapted for the production of
morphine esters.
The process is as follows: To an alcoholic solution of morphine 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 acid ester, the
quantity preferably exceeding one molecule. The reaction commences at once
in a cold condition and is accelerated and terminated by warming on the water
bath.
The isolation of the codeine and small quantities of morphine, which have not
participated in the reaction, is effected by the known methods.
Examples:
1 kilogramme of morphine,
85 grammes of metallic sodium
420 grammes of methyl-sulphate
6000 c. c. m. alcohol,
are heated for some hours in a water bath and the codeine so formed is isolated
by the known methods.
Having now particularly described and ascertained the nature of my said
invention 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 neutral sulphate of methyl or ethyl upon morphine alkali or
morphine alkaline earths in suitable solvents.
1000
HASELTINE, LAKE & Co.,
45, Southampton Buildings, London, W.C., Agents for the Applicant.