Claims:WE CLAIM:

1. The novel compound of Ubiquinol di-Tocopherol succinate ester (I).

Ubiquinol di-Tocopherol succinate ester (I)

2. A process for the preparation of Ubiquinol di-Tocopherol succinate ester (I), comprising the steps of:

a) a-Tocopherol (II) is reacted with succinic anhydride in presence toluene / organic base and catalytic amount of DMAP to obtain Tocopherol succinate (III).

(II) (III)

b) The compound of formula (III) is reacted with Ubiquinol (IV) in presence of organic solvent / organic base and catalytic amount of DMAP to obtain Ubiquinol di-Tocopherol succinate ester (I).

(III)
+
(IV)

Ubiquinol di-Tocopherol succinate ester (I)

3. The process as claimed in claim 1, wherein the organic solvents are selected from ethanol, methanol, isopropyl alcohol, methylene dichloride, ethylene dichloride, dimethyl amino formamide, tetrahydrofuran, toluene, benzene and xylene.

4. The process as claimed in claim 1, wherein the organic bases are selected from methyl amine, triethyl amine, pyridine, phenyl amine, ammonia, tertiary butyl amine.

, Description:DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the novel compound of Ubiquinol di-Tocopherol succinate ester (I). The present invention further provides an improved, commercially viable and industrially advantageous process for the preparation of Ubiquinol di-Tocopherol succinate ester.

In one embodiment of the present invention, provides the novel compound of Ubiquinol di-Tocopherol succinate ester (I).

Another embodiment of the present invention provides an process for the preparation of Ubiquinol di-Tocopherol succinate ester (I), comprising the steps of:

a) a-Tocopherol (II) is reacted with succinic anhydride in presence toluene / organic base and catalytic amount of DMAP to obtain Tocopherol succinate (III).

b) The compound of formula (III) is reacted with Ubiquinol (IV) in presence of organic solvent / organic base and catalytic amount of DMAP to obtain Ubiquinol di-Tocopherol succinate ester (I).

According to the embodiment of the present invention provides an process for the preparation of Ubiquinol di-Tocopherol succinate ester compound of formula I, which comprises solution of a-tocopherol in toluene was added TEA followed by addition of Catalytic DMAP then mixture was stirred at 20-40°C for 5 to 20 min preferably 25-30°C for 5 to 10 min. and then added succinic anhydride heated the reaction mixture at 60-65 °C for 2 hrs to obtain Tocopherol succinate.
Tocopherol succinate is reacted with Ubiquinol in presence of Triethyl amine and catalytic amount of DMAP in dichloromethane was cooled at 0-5°C followed by addition of EDCI HCl then stirred resulting mixture for 5-10 min to obtain Ubiquinol di-Tocopherol succinate ester.

In an embodiment of the present invention provides, wherein the organic solvents are selected from ethanol, methanol, isopropyl alcohol, methylene dichloride, ethylene dichloride, dimethyl amino formamide, tetrahydrofuran, toluene, benzene and xylene.

In an another embodiment of the present invention provides, wherein the organic bases are selected from methyl amine, triethyl amine, pyridine, phenyl amine, ammonia, tertiary butyl amine.

The following examples illustrate the present invention, but should not be construed as limiting the scope of the invention.

EXAMPLES

Example-1:

Preparation of Tocopherol Succinate:

A solution of a-tocopherol (50.0 g) in toluene (5.0 vol) was added TEA (2.9 g, 0.25 m. eq) followed by addition of Catalytic DMAP (0.2 g) then mixture was stirred at 25-30°C for 5 to 10 min then added succinic anhydride (17.5 g, 1.5 m. eq), heated the reaction mixture at 60-65 °C for 2 hrs. The reaction progress was monitored by Qualitative TLC, there after cooled the mixture at 25-30°C and quenched with water (10 V) and extracted the reaction mass in dichloromethane (2 x 10 V) combined organic extract washed with 1.0 N Hydrochloric acid (2 x 4 Vol), evaporated the organic extract under reduced pressure to afford the crude product which was recrystallized in n-hexane to obtain Tocopherol Succinate. (31.0 g, 50%).

1H NMR (400 MHz, CDCl3) d 10.65 (s, 1H), 2.93 (t, 2H), 2.82 (t, 2H), 2.57 (t, 2H), 2.09 (s, 3H), 2.08 (s, 3H), 1.96 (s, 3H), 1.84-1.70 (m, 2H), 1.58-1.49 (m, 3H), 1.48-1.04 (m, 21H), 0.90-0.83 (m, 12H);

13C NMR (100 MHz, CDCl3) d 178.0, 170.9, 149.4, 140.3, 126.6, 124.9, 123.0, 117.3, 75.0, 39.3, 37.4, 37.2, 32.7, 32.6, 31.0, 28.9, 28.5, 27.9, 24.7, 24.4, 22.7, 22.6, 21.0, 20.5, 19.7, 19.6, 12.8, 12.0, 11.79;

MS (ESI) m/z 565.4 (M + Cl).

Example-2:

Preparation of Ubiquinol Di-tcopherol succinate ester:

A solution of Ubiquinol (40.75 g), Triethyl amine (2.0 eq) and catalytic amount of DMAP (0.2 g) in dichloromethane (5.0 vol) was cooled at 0-5°C followed by addition of EDCI HCl (2.2 eq) then stirred resulting mixture for 5-10 min, then added tocopherol succinate (2.0 eq) and further stirred the resulting mixture at 25-30°C for 3 hrs, Reaction progress was monitored by Qualitative TLC, then quenched reaction with water (10 v) and extracted product in dichloromethane (2 x 5 V), combined organic extract was washed with 0.5 N Hydrochloric acid (4 V), distilled the organic layer under reduced pressure to afford the crude product which was further purified by column chromatography by using silica gel (60-120 mesh) and product was eluted in 2-5% ethyl acetate in hexane, distilled the pure fractions to afford the desired product. (25.0 g, 23%)

Example-3:

Preparation of Ubiquinol Di-tocopherol succinate ester:

A solution of Ubiquinol (1.0 g), in dichloromethane (10 V) was added thionyl chloride (2.5 eq) at 0-5°C under nitrogen atmosphere, stirred the mixture for 30 min followed by addition of Triethyl amine (4.0 eq), catalytic amount of DMAP (0.05 g) and Tocopherol succinate (2.0 eq), further stirred the mixture at 25-30°C for 4 hrs, reaction progress was monitored by Qualitative TLC and quenched with water (10 v) and extracted product in dichloromethane (2 x 5 V), combined organic extract was washed with 0.5 N Hydrochloric acid (4 V), distilled the organic layer under reduced pressure to afford the crude product which was further purified by column chromatography by using silica gel (60-120 mesh) and product was eluted in 2-5% ethyl acetate in hexane, distilled the pure fractions to afford the desired product. (0.3 g).

Example-4:

Preparation of Ubiquinol Di-tocopherol succinate ester:

A solution of Tocopherol (2.0 g), in dichloromethane (10 V) was added thionyl chloride (2.5 eq) at 0-5°C under nitrogen atmosphere, stirred the mixture for 30 min followed by addition of Triethyl amine (4.0 eq), catalytic amount of DMAP (0.05 g) and Ubiquinol (1.0 eq), further stirred the mixture at 25-30°C for 4 hrs, reaction progress was monitored by Qualitative TLC and then quenched water (10 v) and extracted product in dichloromethane (2 x 5 V), combined organic extract was washed with 0.5 N Hydrochloric acid (4 V), distilled the organic layer under reduced pressure to afford the crude product which was further purified by column chromatography by using silica gel (60-120 mesh) and product was eluted in 2-5% ethyl acetate in hexane, distilled the pure fractions to afford the desired product. (0.4 g).