Process for the manufacture of a cyclic diester of an alpha-hydroxyacid
Related application : This application claims priority to European application
No. 10169481.8 filed on July 14, 2010, the whole content of this application being
incorporated herein by reference for all purposes.
The present invention relates to a process for the manufacture of a cyclic
diester of an alpha-hydroxyacid. In particular, it relates to the manufacture of lactide
or glycolide, the cyclic diesters of respectively lactic acid and glycolic acid.
Lactide and glycolide are key intermediates for the manufacture of polylactic
acid (or polylactide) (PLA) and polyglycolic acid (or polyglycolide) (PGA), which
are biodegradable, thermoplastic polymers derived from renewable resources. The
synthesis of the lactide and of the glycolide is the most important step in the
conventional PLA and PGA manufacturing processes. It is this step that will govern
the price of the final polymer. The lactide and the glycolide must also be as pure as
possible in order to be able to carry out the ring-opening polymerization leading to
corresponding PLA and PGA with high molecular weights.
The preparation of cyclic diesters of alpha-hydroxyacids is usually conducted
in two distinct steps involving first preparing an oligomer of the alpha-hydroxyacid,
i.e. a relatively short chain condensation polymer thereof having typically a
molecular weight of a few thousands g/mol, then heating the oligomer under
reduced pressure to generate the desired cyclic diester. Such a process is for instance
disclosed in US patent No. 1095205 for lactide synthesis, in US patent No. 2668162
for glycolide synthesis, or in US patent No. 5374743 for both lactide and glycolide
synthesis.
This process has the disadvantage to require a lot of energy and to lead to
impure products requiring further purification steps and the treatment of the by¬
products. A further drawback is linked to the yield of this classical process which is
usually of about 50%, due to the degradation of the oligomers at high temperature.
Direct syntheses of lactide or glycolide have also been disclosed. For example,
US patent No. 3322791 discloses the preparation of lactide by heating lactic acid at
a temperature of 100 to 250°C in the presence of 0.01 to 5 wt%, based on the weight
of lactic acid, of a titanium alkoxide containing up to 2 carbon atoms in the
alkoxide radical. This process seems to be advantageous in view of the classical
polymerization / depolymerization process but the yield is still quite limited, being
of only 60%. Attempts have also been made to synthesize cyclic diesters of alphahydroxyacids
in vapor phase, as disclosed in international patent application
WO92/00292 or W093/ 19058. Such vapor phase processes require specific
equipment and a lot of energy. The degradation as well as the polymerization of the
alpha-hydroxyacid must also be avoided during its vaporization. Another example is
given by international patent application WO93/19058 which discloses the direct
synthesis of cyclic diesters of hydroxyacids, in particular lactide, by removing water
from a feedstream comprising the hydroxyacid until a polymerization degree of less
than or equal to 4 is attained. This process leads to the production of many by
products, requires important additional separation and purification steps and leads to
a very low yield, well below 50%. International patent application WO93/19058
also discloses the possibility to produce cyclic diesters of hydroxyacids by
azeotropic distillation of a diluted solution of the alpha-hydroxyacid in an organic
solvent. Such a method has the main drawback to require the use of a huge amount
of organic solvents, especially aromatic solvents such as benzene or toluene, or of
solvents such as acetonitrile, which is not compatible with an environmental friendly
process. This is especially not compatible with the synthesis of "green" polymers
such as PLA and PGA, manufactured from bio-sourced lactide or glycolide.
Recently, US 2009/0318713 has disclosed a process for the synthesis of lactide by
reacting the calcium or magnesium salt of the lactic acid with a strong acid, the salt
of which with the metal being hygroscopic, to obtain the cyclic diester dispersed in
the hygroscopic salt. This process requires first the preparation of the lactic acid
metal salt. Then, by reacting said lactic acid metal salt with a strong acid, it leads to
a huge amount of salts, such as calcium sulfate, that needs to be treated or destroyed,
which is not environmentally friendly. Another disadvantage of this process is its
low yield, below 50%.
The purpose of the present invention is to provide a process for the synthesis
of cyclic diesters of alpha-hydroxyacids, particularly for the synthesis of lactide and
glycolide, which does not present the above disadvantages. In particular, the purpose
of the present invention is to provide an environmentally friendly, simple and
economic process which enables the manufacture of the cyclic diesters with a high
yield, without numerous subsequent separation and purification steps.
The present invention therefore relates to a process for the manufacture of a
cyclic diester of an alpha-hydroxyacid comprising heating the alpha-hydroxyacid at
a temperature from 100 to 250°C in the presence of at least one polyol and of at least
one catalyst selected from the group consisting carboxylates and alkoxides of Ti, Zr,
Al and Sn.
Indeed, it has been surprisingly found that, when heated in the presence of a
polyol and of a catalyst according to the present invention, the alpha-hydroxyacid
readily forms the corresponding cyclic diester which can be easily separated from
the reaction medium, for example by distillation.
In the process of the present invention, the alpha-hydroxyacid may be any
kind of alpha-hydroxyacid, in particular lactic acid, glycolic acid, glucaric acid,
mandelic acid, malic acid, citric acid and tartaric acid; preferably lactic acid and
glycolic acid; in particular glycolic acid. It has to be noted that all these alphahydroxyacids
can form cyclic diesters. Nevertheless, some differences exist between
the reactivity of these various acids. For instance, when comparing glycolic acid and
lactic acid, it can be seen that glycolic acid comprises a primary alcohol while lactic
acid comprises a secondary alcohol. This difference implies a higher reactivity of
the glycolic acid, which could lead to undue oligomerization of the acid or undue
hydrolization of the glycolide compared to the lactide.
One of the essential features of the present invention resides in the use of the
polyol. It has indeed been found that, in the absence of the polyol, lower yields are
obtained, or even no cyclic diester is produced at all. The polyol may be selected
from the group consisting of ethylene glycol (or monoethylene glycol or glycol),
propylene glycol, diethylene glycol, glycerol, erythritol, mannitol, sorbitol, xylitol,
maltitol, lactitol, and volemitol, preferably from ethylene glycol, propylene glycol,
diethylene glycol, and glycerol, in particular from ethylene glycol. The polyol is
typically added in an amount of from 2 to 50 mol% of the alpha-hydroxyacid,
especially from 5 to 20 mol%, for instance about 10 mol%. Depending on its
molecular weight, the polyol amount is usually from 1 to 40 wt% of the alphahydroxyacid,
particularly from 2 to 20 wt%, more particularly from 3 to 15 wt%, for
example about 5 to 10 wt%.
Another essential feature of the present invention is the choice of the catalyst
which is selected from the group consisting carboxylates (RCOO ) and alkoxides
(RO ) of titanium (Ti), zirconium (Zr), aluminum (Al) and tin (Sn), especially from
titanium carboxylates, titanium alkoxides, tin carboxylates, and tin alkoxides,
particularly from titanium alkoxides. Carboxylates are for example acetates (OAc),
octanoates or ethyl-2-hexanoates. Alkoxides are for example methoxides (OMe),
ethoxides (OEt), propoxides (OPr), isopropoxides (OiPr), n-butoxides (OBu), or
isobutoxides (OiBu). For instance, the catalyst may be selected from titanium
tetraacetate (Ti(OAc) ), titanium tetramethoxide, (Ti(OMe) ), titanium tetraethoxide
(Ti(OEt)4), titanium tetraisopropoxide (Ti(OiPr)4) or tin tetrabutoxide (Sn(OBu)4),
Ti(OEt)4. In the process of the invention, the catalyst is usually added in an amount
of from 5 to 5000 mppm (mol/mol) of the alpha-hydroxyacid, more often from 10 to
500 mppm, most often from 50 to 300 mppm. The catalyst amount is often from 15
to 15000 wppm (wt/wt) of the alpha-hydroxyacid, more often from 30 to 1500
wppm, most often from 100 to 1000 wppm. The catalyst is advantageously added as
a solution in the polyol or as a solution in an optional solvent as defined below.
Without being bound by any theory, it is believed that adding the catalyst as a
solution rather than as a pure product avoids precipitation of the catalyst further to
the hydrolysis of the Ti-OR bond.
In the present process, the alpha-hydroxyacid is typically heated in the
presence of the polyol and of the catalyst at a temperature from 100 to 250°C,
preferably from 150 to 240°C, more preferably from 180 to 230°C. Said heating
may be conducted at atmospheric pressure are under reduced pressure,
advantageously under reduced pressure, in particular under a pressure equal to or
lower than 500 mbar, more particularly equal to or lower than 200 mbar, especially
equal to or lower than 100 mbar. The pressure is generally equal to or higher than 1
mbar, especially equal to or higher than 5 mbar, more particularly equal to or higher
than 10 mbar. In a preferred embodiment, the heating is initiated at atmospheric
pressure then continues under a progressive vacuum until the required pressure is
attained, especially until a pressure from 10 to 100 mbar, for instance about 10, 20,
30, 40 or 50 mbar. The heating time depends upon the reaction temperature and this
parameter may be within wide ranges. Most often, the heating is conducted during 1
to 24 hours, preferably from 2 to 12 hours, more preferably from 4 to 8 hours, for
instance around 6 hours. The reaction is effected preferably in the liquid phase.
Advantageously, the water formed is removed from the reaction mixture, for
instance by distillation.
The heating of the alpha-hydroxyacid in the presence of the polyol and of the
catalyst may be conducted in the presence or in the absence of a solvent. If a solvent
is present, it is usually added in an amount of from 5 to 100 wt% of the reaction
medium, especially of from 10 to 50 wt%. If at least one solvent is added to the
medium comprising the alpha-hydroxyacid, the polyol and the catalyst, it may be
selected from any kind of suitable organic solvent, in particular from polar organic
solvents, more particularly from protic polar organic solvents, especially from
alcohols. In a preferred embodiment, the solvent has a sufficiently high boiling point,
especially a boiling point of at least 80°C, with particular preference a boiling point
of at least 100°C, with a higher preference a boiling point of at least 120°C. In an
especially preferred embodiment, the solvent is more acidic than water, i.e. the
solvent has an acid dissociation constant (pKa) lower than the pKa of water ( 15,7).
Especially suitable solvents are selected from the group consisting of glycol ethers.
Examples of glycol ethers are derivatives of ethylene glycol (R-0-(CH 2-CH2)n-0-R')
or of propylene glycol (R-0-[CH 2-CH(CH2)]n-0-R'), such as ethylene glycol
monomethyl ether (or 2-methoxyethanol or methyl cellosolve), ethylene glycol
monoethyl ether (or 2-ethoxyethanol), ethylene glycol monopropyl ether (or 2-
propoxyethanol), ethylene glycol monoisopropyl ether (or 2-isopropoxyethanol),
ethylene glycol monobutyl ether (or 2-butoxyethanol), ethylene glycol monophenyl
ether (or 2-phenoxyethanol), ethylene glycol monobenzyl ether (or 2-
benzyloxyethanol), diethylene glycol monomethyl ether (or 2-(2-
methoxyethoxy)ethanol or methyl carbitol), diethylene glycol monoethyl ether (or 2-
(2-ethoxyethoxy)ethanol or carbitol cellosolve), diethylene glycol mono-n-butyl
ether (or 2-(2-butoxyethoxy)ethanol), ethylene glycol dimethyl ether (or
dimethoxyethane), ethylene glycol diethyl ether (or diethoxyethane), ethylene glycol
dibutyl ether (or dibutoxyethane), propylene glycol monomethyl ether (or 1-
methoxy-2-propanol), propylene glycol monoethyl ether (or 1-ethoxy-2-propanol),
propylene glycol monopropyl ether (or 1-propoxy-2-propanol), propylene glycol
monobutyl ether, propylene glycol monophenyl ether, dipropylene glycol
monomethyl ether.
The reaction may be conducted in any kind of reactor, for example in an
agitated reactor. In an advantageous embodiment, the reaction can be conducted in a
still or in a distillation apparatus which allows the removal of the water from the
reaction mixture and which allows subsequent separation of the cyclic ester of the
alpha-hydroxyacid from the reaction medium. Distillation systems suitable for this
purpose are common knowledge and are frequently used for separation.
In a preferred embodiment, the alpha-hydroxyacid may be first heated prior to
the addition of the polyol and of the catalyst, typically at a temperature from 80 to
150°C, preferably from 90 to 120°C. Said first heating may for instance be
conducted during 1 to 48 hours, in particular from 12 to 36 hours. Said first heating
is advantageously conducted at atmospheric pressure. Advantageously, water
possibly formed during said heating step is removed from the medium by distillation,
during or after the heating step. It is also possible to add water to the alphahydroxyacid
prior to said first heating, to solubilize the alpha-hydroxyacid. Said
water may be added in an amount of from 10 to 100% by weight of the alphahydroxyacid,
in particular from 30 to 60%, for instance about 40 or 50%. Preferably,
once the alpha-hydroxyacid is solubilized, the water, which includes the added water
as well as water possibly formed during the heating step, is removed from the
medium by distillation during or after the heating step.
After the heating of the alpha-hydroxyacid in the presence of the polyol and of
the catalyst, the cyclic diester of the alpha-hydroxyacid may be collected, for
instance by distillation, especially by distillation under reduced pressure, for
instance by heating the reaction medium at a temperature from 160 to 260°C, for
example from 215 to 240°C, under reduced pressure, for example at a pressure
belowlO mbar, in particular equal to or lower than 5 mbar, especially equal to or
lower than 3 mbar, more preferably equal to or lower than 1 mbar. The cyclic diester
of the alpha-hydroxyacid may also be removed from the reaction mixture by
extraction, for instance using toluene, acetone, tetrahydrofurane or methylene
dichloride as an extraction solvent. This would be followed by evaporation of the
extraction solvent or by crystallization from solution and separation.
The present invention thus also relates to a process for the manufacture of a
cyclic diester of an alpha-hydroxyacid comprising the steps of:
(a) heating the alpha-hydroxyacid at a temperature from 80 to 150°C, during from 1
to 48 hours at atmospheric pressure,
(b) adding at least one polyol and at least one catalyst selected from the group
consisting carboxylates and alkoxides of Ti, Zr, Al and Sn,
(c) heating the mixture at a temperature from 100 to 250°C, the heating being
preferably conducted under reduced pressure, advantageously the heating being
initiated at atmospheric pressure then continued under a progressive vacuum
until a pressure of maximum 200 mbar is attained,
(d) recovering the cyclic diester of the alpha-hydroxyacid by distillation.
The cyclic diester of the alpha-hydroxyacid recovered can be used
immediately for some applications, without further purification steps. The cyclic
diester of the alpha-hydroxyacid may also be purified, for instance by distillation or
chromatographic processes.
The present invention is further illustrated below without limiting the scope
thereto.
Should the disclosure of any patents, patent applications, and publications
which are incorporated herein by reference conflict with the description of the
present application to the extent that it might render a term unclear, the present
description shall take precedence.
Examples
In the following examples, a BfJCHI Glass Oven B-585 was used, equipped
with a boiler (80 ml round-bottomed flask, called Bl) and with a separate vessel in
line with the boiler (called B2). In examples 1 to 6, vessel Bl was fully located in
the oven and vessel B2 was located such that 1/3 was in the oven and 2/3 were out
of the oven. In examples 7-1 1, vessel Bl was fully located in the oven and vessel
was is located out of the oven.
Example 1
17.0 g of pure (99%) solid glycolic acid and 7.6 g of water (to solubilize the
glycolic acid) were introduced into the 80 ml B CHI round-bottomed flask (Bl)
and said flask was placed in a ventilated oven at 110°C during about 80 hours. After
80 hours, a white solid was present in B and 11.1 g of water were collected in B2.
I .4 1 g of distilled ethylene glycol (22.6 mmol or 45 mmol of OH functions)
and 3 mg of a 34 wt% solution of Ti(OEt)4 in methoxyethanol (i.e. 4.4 mg of
Ti(OEt) dissolved in 8.6 mg of methoxyethanol) were added to the white solid.
The mixture was then subjected to the following temperature and pressure profile:
195°C at Patm until melt of the mixture
185°C (2h) at Patm
185°C (lh) at 200 mbar
215°C (30min) at 80 mbar
215°C (lh) at 60 mbar
215°C (lh30) at 3 mbar
205°C (17h) at 3 mbar
I I .6 g of a transparent oil solidifying as a white solid were recovered in vessel
B2 (84 wt% of the reaction medium). 'H-NMR analysis of the content of B2 showed
the following composition: 57% glycolide and 2.3% glycolic acid, the remainder
being glycolic acid oligomers. The global yield in glycolide was 51%.
Example 2
Example 1 was reproduced except that the mixture glycolic acid / water was
kept at 110°C during 60 hours rather than 80 hours (but the same quantity of water
was recovered in B2) and that 32 mg of a 35 wt% solution of Ti(OEt)4 in
methoxyethanol (i.e. 11.4 mg of Ti(OEt)4 dissolved in 20.6 mg of methoxyethanol)
were added, rather than 13 mg of a 34 wt% solution.
11.7 g of a transparent oil solidifying as a white solid were recovered in vessel
B2 (85 wt% of the reaction medium). -NMR analysis of the content of B2 showed
the following composition: 58% glycolide and 2.6% glycolic acid, the remainder
being glycolic acid oligomers. The global yield in glycolide was 52%.
Example 3
Example 2 was reproduced except that the mixture glycolic acid / water was
kept at 110°C during 80 hours rather than 60 hours (but the same quantity of water
was recovered in B2) and that the temperature and pressure profile was modified as
follows:
195°C at Patm until melt of the mixture
185°C (2h) at Patm
185°C (lh) at 200 mbar
185°C (lh) at 60 mbar
185°C (17h) at 3 mbar
7.75 g of a transparent oil solidifying as a white solid were recovered in vessel
B2 (57 wt% of the reaction medium). 1H-NMR analysis of the content of B2
showed the following composition: 61.1% glycolide and 2.4% glycolic acid, the
remainder being glycolic acid oligomers. The global yield in glycolide was 37%.
Example 4 (comparative - no polyol)
17.0 g of pure (99%) solid glycolic acid and 7.5 g of water (to solubilize the
glycolic acid) were introduced into the 80 ml BfJCHI round-bottomed flask (Bl)
and said flask was placed in a ventilated oven at 110°C during about 17 hours. After
80 hours, a white solid was present in Bl and 10.9 g of water were collected in B2.
26 mg of a 34 wt% solution of Ti(OEt)4 in methoxyethanol (i.e. 8.7 mg of
Ti(OEt) 4 dissolved in 17.3 mg of methoxyethanol) were added to the white solid.
The mixture was then subjected to the following temperature and pressure
profile:
215°C (2h) at Patm
215°C (lh) at 200 mbar
215°C (30min) at 80 mbar
215°C (lh) at 60 mbar
215°C (lh30) at 3 mbar
180°C (17h) at 3 mbar
Only 2.3 g of product were recovered in vessel B2 (18 wt% of the reaction
medium), corresponding mainly to glycolic acid.
Example 5 (comparative - no catalyst)
17.0 g of pure (99%) solid glycolic acid, 7.5 g of water (to solubilize the
glycolic acid) and 1.4 g of ethylene glycol (22.6 mmol or 45 mmol of OH functions)
were introduced into the 80 ml BTJCHI round-bottomed flask (Bl) and said flask
was placed in a ventilated oven at 110°C during about 60 hours. After 60 hours, a
white solid was present in Bl and 11.9 g of water were collected in B2.
The mixture was then subjected to the following temperature and pressure
profile:
185°C (2h) at Patm
215°C (lh) at 00 mbar
215°C (30min) at 80 mbar
215°C (lh) at 60 mbar
215°C (3h) at 3 mbar
180°C (17h) at 3 mbar
Only 4.5 g of product were recovered in vessel B2 (32 wt% of the reaction
medium), corresponding mainly to glycolic acid.
Example 6 (comparative - no catalyst)
17.0 g of pure (99%) solid glycolic acid and 7.5 g of water (to solubilize the
glycolic acid) were introduced into the 80 ml BIJCHI round-bottomed flask (Bl)
and said flask was placed in a ventilated oven at 110°C during about 60 hours. After
60 hours, a white solid was present in Bl and 11.0 g of water were collected in B2.
1.41 g of distilled ethylene glycol (22.6 mmol or 45 mmol of OH functions)
were added to the white solid and the mixture was placed in a ventilated oven at
110°C during 15 hours. 1.3 g of water were collected in B2.
The mixture was then subjected to the following temperature and pressure
profile:
195°C (2h) at Patm
215°C (lh) at 200 mbar
215°C (30min) at 80 mbar
215°C (lh) at 60 mbar
215°C (3h) at 3 mbar
180°C (17h) at 3 mbar
Only 1.8 g of product were recovered in vessel B2 (14 wt% of the reaction
medium), corresponding mainly to glycolic acid.
Examples 7-8
17.0 g of pure (99%) solid glycolic acid and 7.6 g of water (to solubilize the
glycolic acid) were introduced into the 80 ml BIJCHI round-bottomed flask (Bl)
and said flask was placed in a ventilated oven at 110°C during about 60 hours. After
60 hours, a white solid was present in B1 and about 1 g of water were collected in
B2.
1.40 g of distilled ethylene glycol (22.5 mmol or 45 mmol of OH functions)
and Ti(OEt) 4 (amounts in the table below, added as 34 wt% solution in
methoxyethanol) were added to the white solid.
The mixture was then subjected to the following temperature and pressure
profile:
195°C at Patm until melt of the mixture (about 30min)
190°C (1.5h) at Patm
190°C (lh) at 200 mbar
215°C (lh) at 80 mbar
225°C (lh30) at 50 mbar
240°C (17-22h) at a pressure below 1 mbar
The duration of the distillation, the amount of catalyst, and the global yield in
glycolide are summarized in the table below.
Examples 9-1 1
Examples 7-8 were reproduced except the temperature and pressure profile
which was as follows:
195°C (2h) at Patm
215°C (lh) at 200 mbar
225°C (2h) at 50 mbar
225°C (2h) at 10 mbar
240°C (17-22h) at a pressure below 1 mbar
The duration of the distillation, the amount of catalyst, and the global yield in
glycolide are summarized in the table below.
Ti(OEt)4 added as 34 wt% solution in methoxyethanol
* Ti(OEt)4 added as a solution in the 1.40 g of ethylene glycol (no methoxyethanol)
C L A I M S
1. A process for the manufacture of a cyclic diester of an alpha-hydroxyacid
comprising heating the alpha-hydroxyacid at a temperature from 100 to 250°C in the
presence of at least one polyol and of at least one catalyst selected from the group
consisting carboxylates and alkoxides of Ti, Zr, Al and Sn.
2. The process according to claim 1, wherein the alpha-hydroxyacid is
selected from the group consisting of lactic acid, glycolic acid, glutaric acid,
mandelic acid, malic acid, citric acid and tartaric acid; preferably lactic acid and
glycolic acid; in particular glycolic acid.
3. The process according to claim 1 or 2, wherein the heating is conducted at
a temperature from 150 to 240°C, preferably from 180 to 230°C.
4. The process according to anyone of claims 1 to 3, wherein the heating is
conducted under reduced pressure, in particular under a pressure equal to or lower
than 500 mbar, more particularly equal to or lower than 200 mbar.
5. The process according to anyone of claims 1 to 4, wherein the heating is
initiated at atmospheric pressure then continues under a progressive vacuum until a
pressure of from 10 to 200 mbar is attained.
6. The process according to anyone of claims 1 to 5, wherein the polyol is
selected from the group consisting of ethylene glycol, propylene glycol, diethylene
glycol, glycerol, erythritol, mannitol, sorbitol, xylitol, maltitol, lactitol, and
volemitol, preferably from ethylene glycol, propylene glycol, diethylene glycol, and
glycerol.
7. The process according to anyone of claims 1 to 6, wherein the polyol is
added in an amount of from 2 to 50 mol % of the alpha-hydroxyacid, especially of
from 5 to 20 mol %.
8. The process according to anyone of claims 1 to 7, wherein the catalyst is
selected from the group consisting of carboxylates and alkoxides of titanium,
zirconium, aluminum and tin, particularly from titanium alkoxides.
9. The process according to anyone of claims 1 to 8, wherein the catalyst is
added in an amount of from 5 to 5000 mppm (mol/mol) of the alpha-hydroxyacid,
more often from 10 to 500 mppm, most often from 50 to 300 mppm.
10. The process according to anyone of claims 1 to 9, wherein the heating is
conducted in the absence of a solvent.
11. The process according to anyone of claims 1 to 10, wherein the heating is
conducted in the presence of at least one organic solvent, in particular in the
presence of at least one polar organic solvent, especially an organic solvent selected
from glycol ethers.
12. The process according to anyone of claims 1 to 11, wherein the solvent is
present in an amount of from 5 to 100 wt% of the reaction medium, especially from
10 to 50 wt%.
13. The process according to anyone of claims 1 to 12, wherein the alphahydroxyacid
is heated at a temperature from 80 to 150°C, preferably from 90 to
120°C, during from 1 to 48 hours, in particular from 12 to 36 hours, prior to the
addition of the polyol and of the catalyst.
14. The process according to claim 13, wherein the heating is conducted at
atmospheric pressure.
15. The process according to anyone of claims 1 to 14, wherein the cyclic
diester of the alpha-hydroxyacid is collected by extraction or by distillation,
especially by distillation under reduced pressure.