CA2073126C

CA2073126C - Preparation of alkylphosphocholines

Info

Publication number: CA2073126C
Application number: CA002073126A
Authority: CA
Inventors: Juergen Engel; Bernd Kutscher; Wolfgang Schumacher; Ulf Niemeyer; Alfred Olbrich; Gerhard Noessner
Original assignee: Asta Medica GmbH
Current assignee: Baxter Healthcare SA; Baxter International Inc
Priority date: 1991-07-04
Filing date: 1992-07-03
Publication date: 2001-09-04
Anticipated expiration: 2012-07-03
Also published as: DK0521297T3; EG20551A; CN1068331A; SG47844A1; NO981742L; IL102379A; AU652646B2; AU663259B2; JP3171279B2; IE80555B1; GR3025490T3; HU219243B; HUT61560A; NO922612D0; FI107260B; JPH05186483A; NO304232B1; CN1034941C; PL295129A1; IE922182A1

Abstract

A process for the preparation of C14 - C18 alkyl-phosphocholines comprises reacting an n-alkanol having a chain length of C14 to C18 with phosphorus oxychloride in a single reaction vessel. The product obtained is reacted with a choline salt in the presence of a basic substance, without isolation and purification, in an inert solvent, to form a corresponding phosphoric acid diester chloride. The phosphoric acid diester chloride is hydrolyzed to obtain the alkylphosphocholine. Purification of C14 - C18 alkylphosphocholines is performed by adding to a solution of an alkylphosphocholine, in a solvent selected from the group consisting of anhydrous alcohols with 1 to 5 carbon atoms, water and any mixture of said alcohols with or without water, a mixed-bed ion-exchanger, or successively or simultaneously at least one ion-exchanger selected from the group consisting of an acid ion-exchanger and a basic ion-exchanger. The solution and the ion-exchanger are stirred together, and the solution is separated from the ion-exchanger to recover purified alkylphosphocholine.

Description

PREPARATION OF ALKYLPHOSPHOCHOLINES
The invention relates to a process for the preparation of alkylphosphocholines, in a two-step process, without intermediate isolation or purification.
Eibl et al. (EP 225,608) describe the preparation and use of alkylphosphocholines for the treatment of tumours. The starting substances used in the Eibl process of preparation are the corresponding n-alcohol and phosphorus oxychloride.
They are reacted in tetrahydrofuran to produce the phosphoric acid ester dichloride. In a second step 2-aminoethanol is reacted with the phosphoric acid ester dichloride to form the 2-hexadecyl-1,3,2-oxaphospholan-2-oxide in dioxan. Hydrolysis with 2N hydrochloric acid yields the open-chain amine which is exhaustively methylated to alkylphosphocholine with dimethyl sulphate in 2-propanol.
This process has the following disadvantages: it is necessary to isolate and purify the intermediate products.
In addition, alkylating reagents are used. The use of potassium carbonate as an auxiliary base in this step of the process leads to the product having a potassium content that is undesirably high for pharmaceutical purposes.
Long-chain alkylphosphocholines having an antimicrobial effect are described by Kanetani et al., Nippon Kayaku Kaushi, 9, 1452 (1984). They are prepared using the following process: ethylene glycol and phosphorus trichloride are reacted to form 2-chloro-1,3,2-dioxaphospholane, the product is purified by distillation and is oxidized with oxygen to form 2-chloro-1,3,2-dioxaphospholane-2-oxide, and then distilled again. The 2-chloro-1,3,2-dioxaphospholane-2-oxide is then reacted with 1-hexadecanol to 2-hexadecyl-1,3,2-dioxaphospholane-2-oxide. The 2-hexadecyl-1,3,2-dioxaphospholane-2-oxide is reacted with trimethylamine in an autoclave to hexadecylphosphocholine, the crude product is purified both with alkaline and with acid ion exchangers, and then is recrystallized from acetone/chloroform. The analogous process is also used to prepare the octyl-, decyl-, dodecyl, tetradecyl and octadecyl derivatives.
The disadvantage of this process is that it is necessary to work with increased pressure in the last step of the process and that the use of trimethylamine constitutes an industrial hygiene problem. It is also a disadvantage that the hydrolysis-sensitive intermediate products 2-chloro-1,3,2-dioxaphospholane, 2-chloro-1,3,2-dioxaphospholane-2-oxide and 2-hexadecyl-2-oxa-1,3,2-dioxaphospholane need to be isolated and purified. In addition, environmentally-unfriendly solvents such as benzene are used, the solvents being changed from step to step.
All known processes use chromatographic methods for working up and purifying the raw products. However, chromatographic working up processes of this kind have the following disadvantages:
- their conversion to an industrial scale causes difficulties since the dimensions of the stationary phase cannot be increased at will, - chromatographic processes are time-consuming.
In accordance with this invention a process for the preparation of C19 - C18 alkylphosphocholines comprises la reacting an n-alkanol having a chain length of C14 to C18 with phosphorus oxychloride in a single reaction vessel;
reacting the product obtained with a choline salt in the presence of a basic substance, without isolation and purification, in an inert solvent, to form a corresponding phosphoric acid diester chloride; and hydrolyzing the phosphoric acid diester chloride to obtain the alkylphosphocholine. The purification of C14 - Cie alkylphosphocholines can be performed in a solvent selected from the group consisting of anhydrous alcohols with 1 to 5 carbon atoms, water and any mixture of the alcohols with or without water. A mixed-bed ion-exchanger, or successively or simultaneously at least one ion-exchanger selected from the group consisting of an acid ion-exchanger and a basic ion-exchanger are added to the solution; followed by stirring the solution and the ion-exchanger together, separating the solution from the ion-exchanger, and recovering purified alkylphosphocholine.
It has surprisingly been found that the process of the invention achieves a higher total yield, despite the use of one less purification step than in previously-known processes. In addition, the invention uses less solvent.
The process of this invention also avoids the use of alkylating reagents such as dimethyl_ sulphate which lead to a high potassium content of the product due to the use of potassium carbonate as an auxiliary base. The potassium content must be kept as low as possible in substances used as pharmaceutically active substances. The process of this invention also avoids the time-consuming chromatographic step during working up. The product purity achieved in the process is greater than in the known processes.

The first step in the conversion consists in the reaction of phosphorus oxychloride with an n-alkanol having a chain length of 14-18 hydrogen atoms. If a solvent is used, it may be a halogenated hydrocarbon, a saturated cyclic ether, an acyclic ether, a saturated hydrocarbon with 5 to 10 carbon atoms, a liquid aromatic hydrocarbon which can also be substituted by halogen (in particular chlorine) or in a mixture of the above-mentioned solvents. However a solvent is not required. Optionally this step may be carried out in the presence of a basic substance conventionally used for this purpose.
Halogenated hydrocarbons that may for example be used are hydrocarbons of 1 to 6 carbons atoms, where one or several or all of the hydrogen atoms are replaced by chlorine atoms. It is for example possible to use methylene chloride, chloroform, ethylene chloride, chlorobenzene.
When halogen-substituted aromatic hydrocarbons are used, these are preferably substituted with 1 or 2 halogen atoms.
Saturated cyclic ethers that may be used are for example ethers with a ring size of 5-6 which consist of carbon atoms and 1 or 2 oxygen atoms. Examples are tetrahydrofuran and dioxan.
The acyclic ethers consist of 2 to 8 carbon atoms and are liquid. Examples that may be considered; diethylether, diisobutylether, methyl-tert.-butylether, diisopropyl ether.

:T, a .o . l r, '~ ~~ ~. ,., :.~
Saturated hydrocarbons that may be considered are unbranched and branched hydrocarbons that consist of 5 to 1~ carbon atoms and are liquid. Examples that may be considered are pentane, hexane, hept~~ne, cyclohexane.
Aromatic hydrocarbons that may for example be considered are benzene and alkyl-substituted benzenes where the alkyl substituents consist of i to 5 carbon atoms.
Basic substances that may be considered both for the reaction of the phosphorus oxychloride with the n-alkanol and also for the subsequent reaction with the choline salt are amines, for example aliphatic amines of the formula NR1R2R3, where R1, R2 and R~ are the same or different and represent hydrogen or Ci-C6-alkyl, aromatic amines such as pyridine, picoline, quinoline.
During the reaction with the choline salt it is possible to use the basic substance required herefor at the same time with the choline salt or also before the choline salt. For the reaction with the choline salt a solvent is needed in any case; in other words, a.f the first reaction step is conducted without a particular solvent, one has to tae added at this stage, The mol ratio of phosphorus oxychloride to the alkanol is for example between 1,5:1 to 1:1.1.
The choline salt is for example used in excess in relation to the alkanol (about i.1 - 1.5 molar excess).
If the reaction of the phosphorus oxychloride with the alkanol occurs in the presence of a basic substance, the amount of the basic substance is for example 1 to 3 Mol related to 1 Mol POC13.
For the subsequent reaction with the choline salt the amount of basic substance used is for example 'I to 5 Mol related to 1 Mol alkanol.

~~'~p~ ~~u The reaction temperature of the reaction of phosphorus oxychloride with n-alkanol lies between -30°C and +30°C, preferably -15°C and +5°C, in particular -10°C and -5°C.
The reaction time of this conversion is for example 0.5-5 hours, preferably 1-3 hours, in particular 1.5-2 hours. If the reaction occurs in the presence of a basic substance, it is generally quick (about 30 minutes).
The choline salt is then added in portions or in its entirety.
Salts of choline that may for example be used are salts with mineral acids (such as sulphuric acid, hydrochloric acid), and also salts of choline with organic acids such as acetic acid, para-toluenesulphonic acid and the like.
This reaction step occurs in an inert solvent. Solvents that may be considered here are the same that are used to react the phosphorus oxychloride with the n-alkanol if this reaction occurs in a solvent.
The basic substance is then dissolved in one of the stated solvents or added dropwise without solvent.
The following are preferably used as solvent for the basic substance: halogenated hydrocarbons, saturated cyclic ethers, acyclic ethers, saturated hydrocarbons with 5 to 10 carbon atoms, liquid aromatic hydrocarbons or mixtures of the above mentioned solvents.
These are the same solvents that may be used for the reaction of phosphorus oxychloride with the n-alkanol.
Addition of the basic substance causes the temperature to rise.
Care must be taken that the temperature is maintained within a range between 0°C to 40°C, preferably 10°C to 30°C, in particular at 15°C to 20°C.

~~~'~~~.2~' The reaction mixture is then still stirred at 5°C to 30°C, preferably 15°C and 25°C (for example 1 hour to 40 hours, preferably 3 hours to 15 hours).
The hydrolysis of the reaction mixture occurs through addition of water, it being necessary to maintain a temperature between 10°C and 30°C, preferably 15°C and 30°C, in particular between 15°C and 20°C.
The previously mentioned hydrolysis liquids can also contain basic substances. Basic substances that may be considered include carbonates and hydrogen carbonates of the alkaline and alkaline earth metals.
To complete the hydrolysis the mixture is then stirred for a further 0.5 hours to 4 hours, preferably 1 to 3 hours, in particular 1.5 to 2.5 hours at 10°C to 30°C, preferably at 15°C
to 25°C, in particular at 18°C to 22°C.
The reaction solution is then washed with a mixture of water and alcohols (preferably aliphatically saturated alcohols with 1 to 4 carbon atoms) which may optionally also contain a basic substance.
The mixing ratio water:alcohol may for example lie between 5 and 0.5, preferably 1-3 (V/V).
Basic substances that may be considered as washing liquid are for example carbonates and hydrogen carbonates of the alkaline and alkaline earth metals as well as ammonia in the form of the aqueous solution. A 3% sodium carbonate solution in water is particularly preferred.
It is then optionally possible to wash the reaction solution with an acid solution.

Acid washing is advantageous to remove not yet reacted basic portions of the reaction solution, in particular when methylene chloride is used as solvent.
The washing solution consists of a mixture of water and alcohols. Mixtures of aliphatically saturated alcohols with 1 to 4 carbon atoms are preferably used, an acid substance also optionally being present. The mixing ratio water:alcohol may for example lie between 5 and 0.5, preferably 1-3 (V/V).
Acid substances that may be considered for the washing liquid are for example mineral acids and organic acids, fox example hydrochloric acid, sulphuric acid or tartaric acid, and citric acid.
A 10% solution of hydrochloric acid in water is particularly preferred.
The mixture is then washed one again with a mixture of water and alcohols. Mixtures of aliphatic saturated alcohols with 1 to 4 carbon atoms are preferably used, it also being possible for a basic substance to be optionally present.
The mixing ratio water:alcohol may for example lie between 5 and 0.5, preferably 1-3.
The washed phases are then combined and dried in conventional manner and the solvent is then removed (preferably under reduced pressure, for example 5-100 mbar) optionally after addition of 1.5-3 litres, preferably 2-2.5 litres of an aliphatic alcohol (related to 1 Bart by weight of dried product). Alcohols that may for example be used are saturated aliphatic alcohols with a chain length of 1 and 5 carbon atoms. The particularly preferred alcohol here is n-butanol, isopropanol. The purpose of this alcohol treatment is to remove the residual water completely.
The product so-obtained can be purified in the conventional manner (e. g. by chromatography, recrystallization).

:~ art a . ~ ', t '. a i_ :.; >..J
An alkylphosphocholine raw product or the solid residue as described above is for example suspended in saturated aliphatic ketones (3-6 carbon atoms), for example acetone, butanone, methyl-tart.-butylketone, stirred for 1 to 4 hours, preferably 2 hours, suction filtered and dried at 20°C to 50°C in a vacuum at Torr to 100 Torr.
The following purification process is, however, particularly preferred:
The product prepurified in this manner is taken up in anhydrous alcohols (C1 to C4) or in alcohols which contain not more than up to 5 percent by weight of water at 20°C to 60°C, preferably 40°C and insoluble constituents filtered off.
Alcohols that may for example be used are methanol, ethanol, isopropanol, butanol, isobutanol.
The prepurified product may also be dissolved in water.
The filtrate obtained is then stirred with a mixed-bed ion exchanger, for example AmberliteR 1~3, for example for 1 to 5 hours, preferably 2 hours at 10°C to 50°C, preferably 20°C.
Instead of a mixed-bed ion exchanger the purification may also be effected simultaneously or successively with an acid ion exchanger and a basic ion exchanger.
Ion exchangers which may also be used are all insoluble solids which contain ion exchanging groups.
Acid ion exchangers are those which contain for example acid groups such as sulphonic acid groups, carboxyl groups. Examples are ion exchangers with su.lphonic acid groups in a polystyrene matrix such as AmberliteR IR 120, DowexR HCR, DuoliteR C
20 or LewatitR S 100.
Weakly acid ion exchangers are for example those which carry carboxylic acid groups on the basis of a polyacrylic acid matrix, such as AmberliteR IRC 76, DuoliteR C 433 or ReliteR CC.

Basic ion exchangers that may for example be considered are those carrying on a polymer matrix (e. g. polystyrene matrix) primary, secondary, tertiary or quaternary amino groups such as DuoliteR A 101, DuoliteR A 102, DuoliteRlS A 348, DuoliteH A 365, DuoliteR A 375, AmberliteH IRA 6?, DuoliteR A 3?5, AmberliteR IItA. 458 and DuoliteR A 132.
Mixed-bed ion exchangers are mixtures of acid and alkaline ion exchanger resins, such as AmberliteR MB1, AmberliteR MB2, AmberliteR MB3 and AmberliteR I~tB6.
It is also possible to use all conventional ion exchangers in the process.
Reference is also made to Ullmann's Encyclopedia of Industrial Chemistry, 5th Edition (1989), Volume A14, p. 450.
Following vacuum suctioning of the ion exchanger resin the mixture is evaporated under reduced pressure (for example 20 Torr to 200 Torr) at 40°C to 70°C and the mixture is then recrystallized from halogenated hydrocarbons or from alcohol/ketone mixtures.
Halogenated hydrocarbons that may for example be considered for the recrystallization are hydrocarbons containing 1 to 6 carbon atoms where one or several or all carbon atoms axe replaced by chlorine atoms.
It is for example possible to use methylene chloride, chloroform, ethylene chloride, chlorobenzene.
Alcohols that may be considered are saturated aliphatic alcohols with 1 to 6 carbon atoms and 1 to 2 hydroxyl groups. Ketones that may be considered are saturated, aliphatic ketones with 3 to 8 carbon atoms.

2, 0 '~ ;~ ~ ~ ~

The mixing ratio alcohol:ketone is 1 to 1-5 (volume/volume).
An ethanol/acetone mixture in the ratio of 1:1 (V/V) is particularly preferred.
The crystals of alkylphosphocholine obtained are suction filtered and if necessary washed for example with saturated hydrocarbons containing 1 to 6 carbon atoms. (Temperature of the washing liquid for example 15 to 30°C).
Drying is effected for example in a vacuum at 40°C to 80°C
over conventional drying agents, for example phosphorus pentoxide or silica gel.
Example 1 Preparation of hexadecyl phosphocholine 1.0 Mol (92 ml) POC13 in 1.5 1 chloroform are added to a 6-litre stirring apparatus under nitrogen and cooled in an ice bath to 5°C. 0.90 Mol (218 g) hexadecanol are dissolved in 700 ml chloroform and added dropwise together with 4.00 Mol (320 ml) pyridine at a temperature of 5 - 12°C. Dropping time: 1.25 hours. The dropping funnel is then flushed with the remaining 300 ml chloroform. After one and a half hours post-stirring at 0 - 5°C, 1.35 Mol (372 g) solid choline tosylate are added and then 400 ml pyridine added dropwise over 15 minutes. This cases the temperature to rise to 20°C. The ice bath is removed and the reaction mixture is stirred at room temperature for 3 hours. For purposes of hydrolysis 150 ml water are added dropwise over 20 minutes, the temperature rising from 25°C to 36°C. After stirring for half an hour, the reaction solution is washed in each case once with 1.50 litres water/methanol (1:1), 1.50 litres 3g sodium carbonate/methanol (1:1) and 1.50 litres water/methanol (1:9). The chloroform phase washed in this manner is dried over sodium sulphate and evaporated in a rotary e~ ": !',i __ ~ 1 __ evaporator in a vacuaxm after addition of 50 ml i-propanol.
n-butanol is added for drying and the mixture is evaporated in a rotary evaparator again.
Purification is carried out as follows:
The residue is suspended in 2.0 litres acetone, stirred for approx. 2 hours, suction filtered and dried at 30°C in a vacuum.
Raw yield: 325 g (87 $). The raw product is taken up in 3.0 litres absolute ethanol and insoluble portions filtered off. The filtrate is stirred for two hours with 1.0 litres mixed-bed ion exchanger Amberlite lMB 3R(FLUICA). After suction filtration of the ion exchanger resin the mixture is evaporated in a rotary evaporator in a vacuum and then recrystallized once from 0.70 litres methylene chlor5.de. Complete crystallization is achieved in the refrigerator. The crystals are suction filtered and washed with pentane. The mixture is then dried in a vacuum at 30°C over phosphorus pentoxide.
Yield 193 g (0.47 Mol, 53 $) The reaction product has a melting point of 241 - 245°C.
Examples 2-5 are prepared according to the same procedure.
Example 2:

D-19390: H3C-(CH2)13-O-~-O-(CH2)2-Id(CH3)3 Mp: 260°C (disintegration) C19H42NO4P (379.52) ~~L: 89 a (chloroform/methanol/ammonia 25$
=70:20:10) r.i ; ~
r at eef ~.i ~ r:!' i_ Rf:0.27 EA: calc. C 60.135 ~3 11.16 N1 3.69 *H20 57.41 11.16 3.52 f~un;d C 57.40 H 11.42 N 3.61$

57.43$ 11.47 3.65 'H-NMR: (250 MHz, CDC13) 6 = 0.90 ppm (t,3H) 3.80 (q,2H) 1.25 (m,22H) 3.85 (m,2H) 1.55 (p,2H) 4.25 (m,2H) 3.40 (s,9H) F~cample 3:
O
e~ +
D-20403: H3C-(CH2)14-O-f-O-(CH2)2-N(CH3)3 ~_ Mp: 244°C (disintegration) C20H44N04p (393.55) TL: 89 a (chloroform/methanol/amrnonia 25~
=70:40:10) Rf:0.49 EA: calc. C 61.04$ H 11.27 N 3.56 *2H20 55.92 11.26 3.26 found C 56.14 H 10.99 N 3.67 55.74 10.85 3.59$
'H-NMR: (250 MHz, CDC13) 6 = 0.90 ppm (t,3H) 3.80 (q,2H) 207~i 1.30 (m,24H) 3.85 (m,2H) 1.55 (p,2H) 4.25 (m,2H) 3.40 (s,9H) Example 4:
O
ei a D-19767: H3C-(CH2)16-O-P-O-(CH2)2-N(CH3)3 D~
Mp: 254 - 256°C
C22H48N04P (421.61) TL: 127 c (I-butanol/glacial acetic- acid/water=60:20:20) Rf:0.34 EA: calc. C 62.68% H 11.48% N 3.32%
*H20 60.11% 11.46% 3.19%
found C 60.2% H 11.7 N 3.1%
60.5% 11.7%
'H-NMR: (250 MHz, CDC13) b = 0.90 ppm (t,3H) 3.80 (q,2H) 1.25 (m,28H) 3.85 (m,2H) 1.60 (p,2H) 4.25 (m,2H) 3.40 (s,9H) Example 5:
O
D-19391: H3C-(CH2)17-O-P-O-(CH2)2-N(CH3)3 QO

~~, Q: r ~t~ ~ .- ,.
e~ .i ~ J

Mp: 258G (disintegration) C23H50Np4p(435.62) TL: 126 -butanol/glaci.alacetic /water=40:10:10) (I acid Rf:0.1 3 EA: calc.C 63.41 H 11.57 N 3.22 *H2~ 60.90 11.55 3.09 found C 60.80 H 11.93 N 3.15 60.83 12.02 3.15 'H-NMR: (250 MHz, CDC13) = 0.90 ppm (t,3H) 3.80 (d,2H) 1 .25 (rts, 30Fi) 3.85 (m, 2H) 1.60 (p,2H) 4.30 (m,2H) 3.40 (s,9H)

Claims

1. A process for the preparation of C14 - C18 alkylphosphocholines, comprising:
reacting an n-alkanol having a chain length of C14 to C18 with phosphorus oxychloride in a single reaction vessel;
reacting the product obtained, without isolation and purification, in an inert solvent, with a choline salt in the presence of a basic substance, to form a corresponding phosphoric acid diester chloride; and hydrolyzing the phosphoric acid diester chloride to obtain the alkylphosphocholine;
wherein the basic substance used is an aliphatic or aromatic amine, and the reaction temperature does not exceed 40°C when the basic substance is added to the reaction mixture containing the choline salt.

2. A process for the preparation and purification of C14 - C18 alkylphosphocholines, comprising:
reacting an n-alkanol having a chain length of C14 to C18 with phosphorus oxychloride in a single reaction vessel;
reacting the product obtained, without isolation and purification, in an inert solvent and at temperature not exceeding 40°C, with a choline salt in the presence of an aliphatic or aromatic amine as a basic substance, to form a corresponding phosphoric acid diester chloride; and hydrolyzing the phosphoric acid diester chloride to obtain the desired alkylphosphocholine;

obtaining a solution of the alkylphosphocholine in a solvent selected from the group consisting of anhydrous alcohols with 1 to 5 carbon atoms, water and any mixture of said alcohols with or without water;
adding a mixed bed ion-exchanger, or successively or simultaneously at least one ion-exchanger selected from the group consisting of an acid ion-exchanger and a basic ion-exchanger;
stirring the solution and the ion-exchanger together;
separating the solution from the ion-exchanger;
optionally sampling and analyzing the solution at any time during the purification process to determine a purification level; and recovering purified alkylphosphocholine.

3. A process according to claim 2, wherein the time of purification of said solution of alkylphosphocholine is from 30 minutes to 48 hours.

4. A process according to claim 2 or 3, wherein the temperature of the alkylphosphocholine solution undergoing purification is from 10°C to the boiling point of the solution.

5. A process according to any one of claims 1 to 4, in which the n-alkanol is reacted with the phosphorus oxychloride in the presence of an inert solvent.

6. A process according to any one of claims 1 to 4, in which the n-alkanol is reacted with the phosphorus oxychloride in the absence of a solvent.

7. A process according to any one of claims 1 to 6, in which the n-alkanol is reacted with the phosphorus oxychloride in the presence of a basic substance.

8. A process according to any one of claims 1 to 6, in which the n-alkanol is reacted with the phosphorus oxychloride in the absence of a basic substance.

9. A process for the purification of C14 - C18 alkylphosphocholines, comprising:
adding to a solution of an alkylphosphocholine, in a solvent selected from the group consisting of anhydrous alcohols with 1 to 5 carbon atoms, water and any mixture of said alcohols with or without water, a mixed-bed ion-exchanger, or successively or simultaneously at least one ion-exchanger selected from the group consisting of an acid ion-exchanger and a basic ion-exchanger;
stirring the solution and the ion-exchanger together;
separating the solution from the ion-exchanger;
optionally sampling and analyzing the solution at anytime during the purification process to determine a purification level; and recovering purified alkylphosphocholine.

10. A purification process according to claim 9, wherein the time of purification of said solution of alkylphosphocholine is from 30 minutes to 48 hours.

11. A purification process according to claim 9 or 10, wherein the temperature of the alkylphosphocholine solution undergoing purification is from 10°C to the boiling point of the solution.