FORM2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention - AN IMPROVED PROCESS FOR THE PREPARATION OF
2, 3, 6,3', 4'- PENTA-O-ACETYLSUCROSE

2. Applicant(s)
(a) NAME :
(b) NATIONALITY :
(c) ADDRESS :

ALEMBIC LIMITED
An Indian Company
Alembic Campus, Alembic Road, Vadodara-390 003, Gujarat, India

3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed:

Field of invention:
The present invention relates to an improved process for the preparation of 2, 3, 6, 3', 4'-Penta-O-acetylsucrose (6-PAS) (V) from sucrose.
2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) is an important intermediate in the preparation of Sucralose. The structural formula of 6-PAS and Sucralose is represented by formula (V) and (I) respectively as given below.


HO
AcO
OAc

OAc

Background of the invention:
Sucralose is a potent sweetener having sweetness several hundred times that of sucrose. It is chemically known as l,6-dichloro-l,6-dideoxy-b-D-fructofuranosyl-4-chloro-4-deoxy-a-galactopyranoside and having formula is C12H19Cl3O8 and molecular weight 397.64. Sucralose is used as sweetner in beverage, as coating tablet, chewing gum and other food products. It is marketed by McNeil under tradename Splenda®
It is also chemically known as 4,r,6'-trichloro-4,r,6'-trideoxygalactosucrose, (hereinafter referred to as "Sucralose") involves the substitution of chlorine atoms in the sucrose molecule in one of the five secondary hydroxyl positions and in two of the three primary hydroxyl positions. This particular selection of positions usually means that any synthetic route must involve the preparation of an intermediate sucrose derivative having the required positions available for chlorination while the other positions are blocked. In particular, the reactive 6-position must not be chlorinated, while the 4-position must be rendered available for chlorination.


A process for preparing Sucralose is set forth in U.S. Pat. No.4,362,869. This process converts sucrose through a number of steps into Sucralose. This process describes the sequential steps of (1) tritylation of sucrose to block the three primary alcohol groups; (2) acetylation of the five secondary alcohol groups as acetates; (3) detritylation of the three primary alcohol groups to deblock them; (4) acetyl migration from the 4-position to the 6-position; (5) chlorinating the desired alcohol groups at positions 4, 1', 6'; and (6) deblocking the remaining five alcohol groups by deacetylation using sodium methoxide in methanol thereby yielding Sucralose.


OCPh,
The schematic representation is as given below (Scheme I)
OAc

AcO
AcO
(VI)
OH
HO ^ \ n OH
Scheme (I)

(IV)

OAc

U.S. Patent No.4801700 discloses a process for preparation of Sucralose which comprise tritylation and acetylation, detritylation, acetyl migration and chlorination followed by deacetylation. In this process, tritylation is done by addition of trityl chloride in 3 portion in the presence of DMF and activated poly-2-vinylpyridine. Detritylation is carried out by passing HCl(g) in toluene wherein 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV) is precipitate out which is recovered by filtration. Acetyl migration is done using t-butylamine in ethylacetate and heptane.


WO2007072496 discloses a process for preparation of Sucralose which comprise tritylation and acetylation, detritylation, acetyl migration and chlorination followed by deacetylation. In this process, tritylation is done by addition of trityl chloride in 3 portion in the presence of DMF and triethyl amine. Detritylation is carried out by passing HCl(g) in chloroform. On addition of aq. Na2CO3 solution at pH 7.5 to 8, 4-PAS and trytinol is extracted in chloroform. The chloroform is removed to give thick pasty mass which is extracted in hot water, saturated with sodium chloride and extracted with methylene chloride 3-4 times. In this process isolation of 4-PAS (IV) at pH 7 and above gives rise to deacylation of 1 position of sucrose ring. This will result in formation of impurity which is carried forward to the next step and finally to Sucralose.
It is therefore, a need to develop a process which not only overcomes the above mentioned problems but also provides easy, simple and industrially applicable process.
The present inventors have directed their research work towards developing a new process which minimizes the formation unwanted impurities. They found that the addition of trityl chloride in portions minimizes the formation of unwanted impurity of tetra isomer and improves the yield and quality of 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (III). They observed that when 4-PAS is isolated at acidic pH (below 4), 4-PAS is not stable and degradation is observed and when 4-PAS is isolated at basic pH (more than 7.2), an impurity formation was observed resulting in low yield and inferior quality of 6-PAS. They found that when 4-PAS is isolated under controlled pH condition being 6 to 6.5, the generation of degradation impurity is minimized. They also improved the yield of 4-PAS (IV) by modified work up procedure in which aq. layer containing 4-PAS is saltified and then extracted in a solvent. Saltification of aq. layer decreases the solubility of 4-PAS (IV) in water and increases the solubility in solvent. Moreover on extraction with solvent, only 4-PAS gets isolated in solvent and impurities remain in aqueous layer, thereby providing pure 4-PAS.
Object of the invention:


A primary object of the present invention is to provide an improved process for the preparation of 6-PAS (V)
Another object of the present invention is to provide an improved process for the preparation of Sucralose (I).
Another object of the present invention is to provide an improved process for the preparation of 6-PAS (V) with improved yield and high purity.
Another object of the present invention is to provide an improved process for the preparation of 6-PAS (V) in which TRISPA (III) is prepared by portion wise addition of trityl chloride which in turn resulting in improved purity and increased yield of 4-PAS
(IV).
Another object of the present invention is to provide an improved process for the preparation of 6-PAS (V) in which isolation of 4-PAS (IV) is carried out at pH of 6.0 to 6.5 resulting in improved purity and increased yield of 4-PAS (IV).
Yet another object of the present invention is to provide an improved process for the preparation of 6-PAS, which is simple, easy to handle and feasible at commercial scale.
Summary of the invention:
In one aspect, present invention provides a process for the preparation of 2, 3, 6, 3', 4'-Penta-O-acetylsucrose (6-PAS) (V) comprising steps of
(i) Titylation and acetylation of sucrose to give 6, 1', 6'-Tri-0-tritylsucrose
pentaacetate (TRISPA) (III); (ii) Detritylation of 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (III) to give 2,
3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV); (iii) Acetyl migration from 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV) to give
2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) (V).


wherein the improvement comprising effecting the tritylation step by portion wise addition of trityl chloride in six equal portions; and effecting the isolation of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) step at pH 6 to 6.5 by saturating aq. layer with sodium chloride followed by extraction of 2, 3. 4, 3, 4’-Penta-0-acetylsucrose (4-PAS) into organic solvent.
In a further aspect, present invention provides a process for the preparation of Sucralose (I) comprising steps of
(a) Titylation and acetylation of sucrose to give 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (III);
(b) Detritylation of 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (III) to give 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV);
(c) Acetyl migration from 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV) to give 2. 3. 6. 3\ 4*-Penta-0-acetylsucrose (6-PAS) (V);
(d) chlorination of 2. 3. 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) (V) to give 4,1 ',6'-trichloro-4,r,6'-trideoxy galactosucrose penta-acetate (TOSPA) (VI);
(e) Deacetylation of 4,r,6'-trichloro-4,r,6'-trideoxy galactosucrose penta-acetate (TOSPA) (VI) to give Sucralose (I)
wherein the improvement comprising effecting the tritylation step by portion wise addition of trityl chloride in six equal portions; and effecting the isolation of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) step at pH 6 to 6.5 by saturating aq. layer with sodium chloride followed by extraction of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) into organic solvent.
Detailed description of the invention:
The synthetic scheme is as shown below (Scheme I).







OH
OCPh3
HO-
OCPh3
1 .Trity chloride
HO-
AcO _ „
OAc o
(III) 6,1',6'-tri-0-tritylsucrose
pentaacetate OAC
dry HCI(g)
t-butylamine ACO
Chlorinating reagent
(V) 2,3,6,3',4'-Penta- 0Ac O-acetylsucrose
OAc
Deacetylation
-*■ HO
4,1',6'-trichloro- 4,1',6'-trideoxy galactosucrose pentaacetate 0Ac (VI)

AcO
OAc O
(IV) 2,3,4,3',4'-Penta
0H O-acetylsucrose 0Ac
OH O'
(') sucralose OH

OCPh3

Scheme I
A process for the preparation of 2, 3, 6, 3', 4'-Penta-O-acetylsucrose (6-PAS) (V) comprising steps of
(a) preparing a mixture of sucrose and pyridine, heating it to 50°C to 55°C, adding trityl chloride successively in six equal portions in approximately 3.5 hours, continuing stirring and heating for 7 to 8 hours, cooling the reaction mixture to 25°C to 30°C, stirring for 11 to 12 hours at 25°C to 30°C, adding acetic anhydride, heating the reaction mixture to 60°C to 65 °C for 4 to 5 hours, distilling pyridine under vacuum at 55°C to 60°C, cooling the reaction mixture to 10°C to 15°C. precipitating by adding methanol, separating and washing the solid with methanol, drying the solid at 40°C to 45°C till constant weight to obtain TRISPA;
(b) dissolving dry TRISPA in toluene, cooling the clear solution to -6°C to -8°C, passing dry HC1 gas through the solution, to obtain a reaction mixture having temperature of -5°C to 0°C, adding aqueous Sodium bicarbonate solution to the reaction mixture under constant stirring till pH 6 to 6.5, water is added and separating the aq. layer containing 4-PAS, saturating aq. layer with sodium chloride, extracting the saturated solution with methylene chloride, separating


methylene chloride, repeating it 3-4 times, combining methylene chloride, distilling the methylene chloride layer to obtain the solid 4-PAS; (c) adding ethyl acetate and n-hexane to 4-PAS, heating the mixture to 33°C to 35°C till residue is dissolved, adding t-butyl amine and heating the reaction mixture at 33°C to 35°C for 16 to 18 hours, cooling the reaction mixture to 20°C to 30°C, adding n-hexane to obtain solid, separating the solid and washing with n-hexane, drying at 40°C to 45°C till constant weight to obtain 6-PAS;
A process for the preparation of Sucralose (I) comprising steps of
(a) preparing a mixture of sucrose and pyridine, heating it to 50°C to 55°C, adding trityl chloride successively in six equal portions in approximately 3.5 hours, continuing stirring and heating for 7 to 8 hours, cooling the reaction mixture to 25°C to 30°C, stirring for 11 to 12 hours at 25°C to 30°C, adding acetic anhydride, heating the reaction mixture to 60°C to 65 °C for 4 to 5 hours, distilling pyridine under vacuum at 55°C to 60°C, cooling the reaction mixture to 10°C to 1 5°C. precipitating by adding methanol, separating and washing the solid with methanol, drying the solid at 40°C to 45°C till constant weight to obtain TRISPA;
(b) dissolving dry TRISPA in toluene, cooling the clear solution to -6°C to -8°C, passing dry HC1 gas through the solution, to obtain a reaction mixture having temperature of -5°C to 0°C, adding aqueous Sodium bicarbonate solution to the reaction mixture under constant stirring till pH 6 to 6.5, water is added and separating the aq. layer containing 4-PAS, saturating aq. layer with sodium chloride, extracting the saturated solution with methylene chloride, separating methylene chloride, repeating it 3-4 times, combining methylene chloride, distilling the methylene chloride layer to obtain the solid 4-PAS;
(c) adding ethyl acetate and n-hexane to 4-PAS, heating the mixture to 33°C to 35°C till residue is dissolved, adding t-butyl amine and heating the reaction mixture at 33°C to 35°C for 16 to 18 hours, cooling the reaction mixture to 20°C to 30°C, adding n-hexane to obtain solid, separating the solid and washing with n-hexane, drying at 40°C to 45°C till constant weight to obtain 6-PAS;
(d) chlorinating 6-PAS using chlorinating reagent to obtain TOPSA;
(e) deacetylating TOPSA to obtain Sucralose.


In a process for the preparation of TRISPA (III) trityl chloride is added in six equal portions in approximately 3.5 hours in to a solution of sucrose wherein first four portions are added at an interval of 30 min and last two portions are added at an interval of 45 min. The organic solvent used to isolate 4-PAS is selected from methylene chloride, dichloroethane, chloroform, ethylacetate or any other water immiscible solvent in which 4-PAS is extracted.
The following tables showing comparison of results obtained by prior art process and process of the present invention clearly distinguish the advantages of the present invention in respect of yield and purity.
Table-1: Comparison of results obtained by portion wise addition of trityl chloride

Process Yield HPLC Purity
Prior art process (at once trityl chloride addition) 60% 89.5%
Present invention process (portion wise trityl chloride addition in three lots) 62% 93%
Present invention process (portion wise trityl chloride addition in six lots) 74% 94.5%
Table-2: Comparison of results obtained by different extraction process

Process Yield HPLC Purity
Prior art process (single extraction) 69.5% 90%
Present invention process (repeated extraction after salification) 74.5% 98%


Table-3: Comparison of results obtained in recovery of 4-PAS at various pH levels.

Process Yield HPLC Purity
Prior art process (pH=7.5 to 8) 80% 65%
Present invention process (pH=6 to 6.5) 74.5% 98%
The process of the present invention is described by the following examples, which are illustrative only and should not be construed so as to limit the scope of the invention in any manner.
Example-1
Preparation of 6,1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (HI)
A mixture of Sucrose (250g) and pyridine (750ml) was heated at 50°C to 55°C. Trityl chloride (676.57g) was added in 6 portions. 4 portions were added at 30 min. interval, and last 2 portions were added at 45 min. interval. The reaction mass was stirred for 7 to 8 hrs at 50°C to 55°C. The reaction mass was cooled to 25°C to 30°C and stirred further for 11 to 12 hr. Acetic anhydride (690 ml) was added to the reaction mixture and heated to 60°C to 65°C for 4 to 5 hr. The solvent (approx 420 ml) was distilled out solvent under reduced pressure at 55 to 60°C. The reaction mixture was cooled to 10°C to l5°C. Methanol (1.250L) was slowly added to it and stirred for 2 hrs at 10°C to 15°C. Resulting solid was filtered, washed with methanol (250 ml x 2) and dried under vacuum at 40°C to 45 °C for 12 hr to give solid product (700 g) Purity by HPLC: 97 % Yield: 2.8% w/w
Example-2
Preparation of Preparation of 2, 3, 4,3', 4'-Penta-0-acetylsucrose (4-PAS)
A stirred solution of TRISPA (150 g) in Toluene (1500 ml) was cooled to -6°C to -8°C. Dry HCl(g) was bubbled slowly through reaction at the same temperature. The progress of the reaction was monitored on TLC till no unreacterd TRISPA was found. HCl(g) purging was stopped and Nitrogen(g) was purged through reaction mass at -5 to 0 °C for 90 min. Water (900 ml) was added to it and stirred for 5 min. 4% Bicarbonate solution


(approx 100 ml) was added to the reaction mixture to adjust pH at about 6 to 6.5. Water was added to the reaction mixture to make the volume of aqueous layer up to 1.050L. The mixture was stirred for 10 min and then layers were separated. Sodium chloride (100 gm) was added to the aqueous layer, stirred for 10 min, methylene chloride (500 ml) was added and extracted. Organic layer was separated. Again added sodium chloride (20g) to the aqueous layer and stir for 10 min, methylene chloride (500 ml) was added and extracted. The above step is repeated using sodium chloride (20g) and methylene chloride (200ml). All the methylene chloride layers were combined and distilled out under reduced pressure at 40°C to 50°C. The solid was degased for 30 min by applying high vacuum.
Example-3
Preparation of 2,3, 6,3', 4'-Penta-0-acetylsucrose (6-PAS)
To the crude product 4-PAS obtained in the above step, ethyl acetate (150 ml) and hexane (75 ml) was added at 25°C to30°C. The reaction mixture was heated at 33°C to 35°C. The reaction mixture was stirred for about 20 minutes till clear solution. To the reaction mixture, t-Butyl amine (6.5 ml) was added at 33°C to 35°C. The reaction mixture was stirred for 16-18 hr at the same temperature. The progress of the reaction was monitored on TLC to check unreacted TRISPA. The reaction mixture was cooled to 25°C to 30°C. n-Hexane (150 ml) was added slowly within 30 min and stirred the mixture for 2 hr at 25°C to 30°C. The reaction mixture was cooled to 8°C tol0°C and stirred for 30 min. The solid was filtered, washed with n-Hexane (75 ml x 2) and dried under vacuum at 40°C to 45°C for 12 hr to get solid product (53 g). Purity by HPLC: 99 % Yield: 0.35% w/w


We Claim:

1. A process for the preparation of 2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) (V)
OAc
OAc

comprising steps of
(i) Titylation and acetylation of sucrose to give 6, 1', 6'-Tri-0-tritylsucrose
pentaacetate (TRISPA) (III);
AcO
OCPh,
AcO
OCPh3
OCPh3

(ii) Detritylation of 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (III) to give 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV);

AcO
AcO-

(iii) Acetyl migration from 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV) to give 2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) (V).

OAc
OAC



wherein the improvement comprising effecting the tritylation step by portion wise addition of trityl chloride in six equal portions; and effecting the isolation of 2, 3, 4, 3, 4’-Penta-0-acetylsucrose (4-PAS) step at pH 6 to 6.5 by saturating aq. layer with sodium chloride followed by extraction of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) into organic solvent.

A process for the preparation of Sucralose (I)
OH
OH

comprising steps of
(i) Titylation and acetylation of sucrose to give 6, 1', 6'-Tri-0-tritylsucrose
pentaacetate (TRISPA) (III);

AcO
OCPh-,
AcO
OCPh3
OCPh3

(ii) Detritylation of 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) (III) to give 2, 3. 4. 3". 4'-Penta-0-acetylsucrose (4-PAS) (IV);


AcO
AcO

Acetyl migration from 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) (IV) to give 2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) (V);


OAc
HO
OAc

(iv) chlorination of 2, 3, 6, 3', 4'-Penta-O-acetylsucrose (6-PAS) (V) to give 4,1',6'-trichloro-4,1,6'-trideoxy galactosucrose penta-acetate (TOSPA) (VI);

(v) Deacetylation of 4,1.6'-trichloro-4,l .6'-trideoxy galactosucrose penta-acetate (TOSPA) (VI) to give Sucralose (I).
wherein the improvement comprising effecting the tritylation step by portion wise addition of trityl chloride in six equal portions; and effecting the isolation of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) step at pH 6 to 6.5 by saturating aq. layer with sodium chloride followed by extraction of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) into organic solvent.
3. The process as claimed in claim 1 or 2, wherein the organic solvent used in isolation of 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS) is selected from methylene chloride, dichloroethane, chloroform, ethylacetate or mixture thereof.
4. A process for the preparation of 2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS) (V) comprising,
(a) preparing a mixture of sucrose and pyridine, heating it to 50°C to 55°C, adding trityl chloride successively in six equal portions in approximately 3.5 hours, continuing stirring and heating for 7 to 8 hours, cooling the reaction mixture to 25°C to 30°C, stirring for 11 to 12 hours at 25°C to 30°C, adding acetic anhydride, heating the reaction mixture to 60°C to 65°C for 4 to 5 hours, distilling pyridine under vacuum at 55°C to 60°C, cooling the reaction mixture to 10°C to


15°C, precipitating by adding methanol, separating and washing the solid with methanol, drying the solid at 40°C to 45°C till constant weight to obtain 6, 1', 6'-Tri-O-tritylsucrose pentaacetate (TRISPA);
(b) dissolving dry 6, 1', 6*-Tri-0-tritylsucrose pentaacetate (TRISPA) in toluene, cooling the clear solution to -6°C to -8°C, passing dry HC1 gas through the solution, to obtain a reaction mixture having temperature of -5°C to 0°C, adding aqueous Sodium bicarbonate solution to the reaction mixture under constant stirring till pH 6 to 6.5, water is added and separating the aq. layer containing 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS), saturating aq. layer with sodium chloride, extracting the saturated solution with methylene chloride, separating methylene chloride, repeating it 3-4 times, combining methylene chloride, distilling the methylene chloride layer to obtain the solid 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS);
(c) adding ethyl acetate and n-hexane to 2. 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS), heating the mixture to 33°C to 35°C till residue is dissolved, adding t-butyl amine and heating the reaction mixture at 33°C to 35°C for 16 to 18 hours, cooling the reaction mixture to 20°C to 30°C, adding n-hexane to obtain solid, separating the solid and washing with n-hexane, drying at 40°C to 45°C till constant weight to obtain 2, 3, 6, 3', 4'-Penta-0-acetylsucrose (6-PAS);
5. A process for the preparation of Sucralose (I) comprising,
(a) preparing a mixture of sucrose and pyridine, heating it to 50°C to 55°C, adding trityl chloride successively in six equal portions in approximately 3.5 hours, continuing stirring and heating for 7 to 8 hours, cooling the reaction mixture to 25°C to 30°C, stirring for 11 to 12 hours at 25°C to 30°C, adding acetic anhydride, heating the reaction mixture to 60°C to 65°C for 4 to 5 hours, distilling pyridine under vacuum at 55°C to 60°C, cooling the reaction mixture to 10°C to 15°C, precipitating by adding methanol, separating and washing the solid with methanol, drying the solid at 40°C to 45°C till constant weight to obtain 6, 1', 6'-Tri-O-tritylsucrose pentaacetate (TRISPA);
(b) dissolving dry 6, 1', 6'-Tri-0-tritylsucrose pentaacetate (TRISPA) in toluene, cooling the clear solution to -6°C to -8°C, passing dry HC1 gas through the


solution, to obtain a reaction mixture having temperature of -5°C to 0°C, adding aqueous Sodium bicarbonate solution to the reaction mixture under constant stirring till pH 6 to 6.5, water is added and separating the aq. layer containing 2, 3, 4. 3’. 4'-Penta-0-acetylsucrose (4-PAS), saturating aq. layer with sodium chloride, extracting the saturated solution with methylene chloride, separating methylene chloride, repeating it 3-4 times, combining methylene chloride, distilling the methylene chloride layer to obtain the solid 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS);
(c) adding ethyl acetate and n-hexane to 2, 3, 4, 3', 4'-Penta-0-acetylsucrose (4-PAS), heating the mixture to 33°C to 35°C till residue is dissolved, adding t-butyl amine and heating the reaction mixture at 33°C to 35°C for 16 to 18 hours, cooling the reaction mixture to 20°C to 30°C, adding n-hexane to obtain solid, separating the solid and washing with n-hexane, drying at 40°C to 45°C till constant weight to obtain 2. 3. 6, 3\ 4'-Penta-0-acetylsucrose (6-PAS);
(d) chlorinating 2, 3, 6, 3\ 4'-Penta-0-acetylsucrose (6-PAS) using chlorinating reagent to obtain 4,1,6'-trichloro-4,r,6'-trideoxy galactosucrose penta-acetate (TOSPA);
(e) deacetylating 4,r,6'-trichloro-4,l',6'-trideoxy galactosucrose penta-acetate (TOSPA) to obtain Sucralose.
Dated this 21st day of December 2007



Title : AN IMPROVED PROCESS FOR THE PREPARATION OF 2, 3, 6, 3', 4'- PENTA-O-ACETYLSUCROSE
ABSTRACT
The present invention relates to an improved process for the preparation of 2, 3, 6, 3', 4'-Penta-O-acetylsucrose (6-PAS) (V) from sucrose.

OAc

OAc