DESC:FIELD OF THE INVENTION

Present invention provides a novel process for the preparation of Perfluorohexyloctane with high yield and purity. Present invention also provides process for the purification of Perfluorohexyloctane.

BACKGROUND OF THE INVENTION

Semifluorinated alkanes are physically, chemically and physiologically inert compounds, which find application in medicine, in particular in the ophthalmic and dermatological field.

The chemical name of Perfluorohexyloctane is 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-tetradecane, and its structure is given by the following formula I

OBJECT OF THE INVENTION

Main object of the present invention is to provide a novel process for the preparation of Perfluorohexyloctane with high yield and purity.

Another object of the present invention is to provide a process for the purification of Perfluorohexyloctane.

SUMMARY OF THE INVENTION

Main aspect of the present invention provides a novel process for the preparation of Perfluorohexyloctane of Formula I with high yield and purity.

Another aspect of the present invention provides a process for the purification of Perfluorohexyloctane.

Another aspect of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I,
,
comprising, reducing 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodotetradecane of Formula II

in the presence of suitable reducing agent to give compound of formula I.

Another aspect of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I,

comprising the steps of:
a) reacting Perfluorohexyliodide of formula III

,
with a compound of Formula IV

in the presence of suitable solvent to give an intermediate compound of formula II;

b) reducing the compound of Formula II using suitable reducing agents to give compound of Formula I; and
c) optionally purifying compound of Perfluorohexyloctane of Formula I.

Another aspect of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I, comprising the steps of:
a) reacting perfluoro hexyl iodide of formula III

with compound of Formula IV

in the presence of suitable solvent to give an intermediate compound of formula II;

b) converting the compound of Formula II to compound of Formula IIa
;
c) reducing compound of Formula IIa using suitable reducing agent to get compound of Formula I; and
d) optionally purifying compound of Perfluorohexyloctane of Formula I.

Another aspect of the present invention provides a process for the purification of Perfluorohexyloctane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) optionally, heating the reaction mass;
c) optionally, cooling the reaction mass; and
d) isolating pure compound of Formula I.

Another aspect of the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) cooling the reaction mass; and
c) isolating pure compound of Formula I.

Another aspect of the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) heating the reaction mass;
c) optionally, cooling the reaction mass; and
d) isolating pure compound of Formula I.

Another aspect of the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) cool the reaction mass;
c) filter the reaction mass to obtain residue;
d) adding one or more suitable solvent to the residue;
e) heating the reaction mass; and
f) isolating pure compound of Formula I.

In another embodiment, the present invention provides a purification process of compound of Formula I, comprising the steps of:
a) providing a solution or dispersion of compound of Formula I in one or more suitable solvents;
b) adding one or more suitable solvents to reaction mass of step a);
c) optionally, heating the reaction mass of step a) or step b); and
d) isolating pure compound of Formula I.

Another aspect of the present invention provides substantially pure Perfluorohexyloctane compound of Formula I.

DETAILED DESCRIPTION OF THE INVENTION

The term “substantially free” used in the context of the present invention means material having each impurity less than about 0.3% by area percentage of HPLC. In particular, less than about 0.15% by area percentage of HPLC. More particular, not in detectable amount by area percentage of HPLC.

The term "Substantially pure" as used herein refers to the purity of the material which is at least about 85.0%, at least about 90%, at least about 95.0%, at least about 98%, at least about 99%, at least about 99.5% or at least about 99.9 % as measured by a HPLC.

“Suitable acid” or “acid” as used in the context of the present invention refers to inorganic acids such as hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid salt; organic acids such as succinic acid, formic acids, acetic acid, diphenyl acetic acid, triphenylacetic acid, caprylic acid, dichloroacetic acid, trifluoro acetic acid, propionic acid, butyric acid, lactic acid, citric acid, gluconic acid, mandelic acid, tartaric acid, malic acid, adipic acid, aspartic acid, fumaric acid, glutamic acid, maleic acid, malonic acid, benzoic acid, p-chlorobenzoic acid, nicotinic acid, o-hydroxybenzoic acid, p-hydroxybenzoic acid, 1-hydroxy-naphthalene-2-carboxylic acid, hydroxynaphthalene-2-carboxylic acid, ethanesulfonic acid, ethane-1,2-disulfonic acid, 2-hydroxyethane sulfonic acid, methanesulfonic acid, (+)-camphor-10-sulfonic acid, benzenesulfonic acid, naphthalene-2-sulfonic acid, p-toluenesulfonic acid; and the like.

In the context of the present invention, the term “reaction mixture” or “reaction mass” are used for the present invention are comprises, but not limited to clear solution, partially dissolved solution, suspension, slurry, turbid solution, mixture, biphasic solution or any other phase as known in the literature.

In the context of the present invention, the term “suitable solvent” or “solvent” provides solvents are selected from the group comprising of, but are not limited to, C1-C6 alcohols, C1-C8 hydrocarbons, halogenated hydrocarbons, ethers, C3-C8 ketones, esters, nitriles, sulphonamides, acetamides, pyrrolidines, formamides, water and mixture thereof. For Example, some of the suitable solvents comprises of methanol, ethanol, butanol, t-butanol, isopropyl alcohol, n-propyl alcohol, iso-butanol, pentanol, glycols, toluene, xylene, chlorobenzene, acetonitrile, propionitrile, dimethyl acetamide (DMA), dimethylformamide (DMF), N-methyl pyrrolidine (NMP), dimethyl sulfoxide (DMSO), hexamethyl phosphoramide (HMPA), dimethyl ether, diethyl ether, diisopropyl ether, petroleum ether, tetrahydrofuran (THF), methyl tetrahydrofuran, dioxane, acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), methyl t-butyl ketone, dichloromethane, dichloroethane, chloroform, tetrachloromethane, chlorobenzene, ethyl acetate, propyl acetate, propenyl acetate, t-butyl acetate, hexane, n-heptane, cyclohexane, cycloheptane, petroleum benzine, water and mixture thereof.

The purpose of the present invention is to provide an economical, industrially efficient, and convenient process for the production of Perfluorohexyloctane with high yield and is suitable for large-scale production.

Main embodiment of the present invention provides a novel process for the preparation of Perfluorohexyloctane of Formula I which has excellent economic efficiency that gives Perfluorohexyloctane with high purity and yield.

Another embodiment of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I.

Another embodiment of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I

comprising, reducing 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodotetradecane of Formula II,

in the presence of suitable reducing agent to give compound of formula I.

Another embodiment of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I,

comprising, reducing 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodotetradecane of Formula II

in the presence of suitable reducing agent and base to give compound of formula I.

Another embodiment of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I,

comprising, reducing 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodotetradecane of Formula II,

in the presence of suitable reducing agent and organic base to give compound of formula I.

Another embodiment of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I, comprising the steps of:
a) reacting perfluoro hexyl iodide of formula III

with compound of Formula IV

in the presence of suitable solvent to give an intermediate compound of formula II;

b) reducing compound of Formula II using suitable reducing agent and base to get compound of Formula I; and
c) optionally purifying compound of Perfluorohexyloctane of Formula I.

Another embodiment of the present invention provides a process for the preparation of Perfluorohexyloctane of Formula I, comprising the steps of:
a) reacting perfluoro hexyl iodide of formula III

with compound of Formula IV

in the presence of suitable solvent to give an intermediate compound of formula II;

b) converting the compound of Formula II to compound of Formula IIa
;
c) reducing compound of Formula IIa using suitable reducing agent to get compound of Formula I; and
d) optionally purifying compound of Perfluorohexyloctane of Formula I.

In another embodiment, conversion of compound of Formula II to compound of Formula IIa is carried out in the presence of a base selected from sodium hydroxide, potassium hydroxide and lithium hydroxide.

In another embodiment, the present invention provides a process for the preparation of compound of formula I, comprising reducing the compound of formula II

in the presence of palladium on carbon, diisopropylethylamine as a base and solvent comprises ethanol to give compound of formula I.

In another embodiment, the present invention provides a process for the preparation of compound of formula I,
comprising, reducing the compound of formula II

in the presence of zinc and solvent comprises acetic acid, ethanol, water or mixture thereof to give compound of formula I.

In another embodiment, reaction of compound of formula III and IV is carried out in the presence of a reagent selected from Azobisisobutyronitrile (AIBN), 2,2'-Azobis (2,4 dimethylvaleronitrile) (ABVN), 2,2'-Azobis(2-methylpropionamidine)dihydrochloride) (AIBA), 2,2’-Azobis(2-(2-imidazolin-2-yl) propane)dihydrochloride (AIBI), 2,2’-Azobis(2-methylbutyronitrile) (AIBN), benzoyl peroxide acetyl peroxide,tert-butyl perbenzoate, and di-tert-butyl peroxide (tBuO-O-tBu) or mixtures thereof.

In preferred embodiment, the one or more suitable solvent used in the preparation of compounds of formulae II, IIa and I is selected from methanol, ethanol, isopropanol, n-propanol, tetrahydrofuran, dimethyl acetamide (DMA), dimethylformamide (DMF), N-methyl pyrrolidine (NMP), dimethyl sulfoxide (DMSO), dioxane, acetone, n-pentane, n-heptane, dimethyl ether, diethyl ether, diisopropyl ether, dioxane and water or mixture thereof.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) optionally, heating the reaction mass;
c) optionally, cooling the reaction mass; and
d) isolating pure compound of Formula I.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) optionally, heating the reaction mass;
c) optionally, cooling the reaction mass; and
d) isolating pure compound of Formula I.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one more suitable to the compound of Formula I to get reaction mass;
b) heating the reaction mass; and
c) isolating pure compound of Formula I.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvents to the compound of Formula I to get reaction mass;
b) cooling the reaction mass; and
c) isolating pure compound of Formula I.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) cooling the reaction mass at -20 to -80 °C; and
c) filtering the reaction mass to get pure compound of Formula I.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) cool the reaction mass;
c) filter the reaction mass to obtain residue;
d) adding one or more suitable solvent to the residue;
e) heating the reaction mass; and
f) isolating pure compound of Formula I.

In another embodiment, the present invention provides a process for the purification of Perfluorohexyl octane of Formula I, comprising the steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) cool the reaction mass at -20 to -80 °C;
c) filter the reaction mass to obtain residue;
d) adding one or more suitable solvent to the residue;
e) heating the reaction mass at 50 to 70 °C; and
f) distilling the solvent to get pure compound of Formula I.

In another embodiment, the present invention provides a purification process of compound of Formula I, comprising the steps of:
a) providing a solution or dispersion of compound of Formula I in one or more suitable solvents;
b) adding one or more suitable solvents to reaction mass of step a);
c) optionally, heating the reaction mass of step a) or step b); and
d) isolating pure compound of Formula I.

In preferred embodiment, the one or more suitable solvent used in step b) of the purification process of compound of Formula I act as anti-solvent for the one or more suitable solvent used in step a).

In preferred embodiment, the one or more suitable solvent used in the purification of compound of Formula I is selected from methanol, ethanol, isopropanol, n-propanol, acetone, n-heptane, n-pentane, tetrahydrofuran, dimethyl ether, diethyl ether, diisopropyl ether, dioxane and water or mixture thereof.

In another embodiment, the present invention provides a process for the purification of compound of Formula I, comprising:
a) providing a solution of compound of Formula, I in one or more suitable solvents; and
b) purifying the compound of Formula, I using suitable chromatography.

In another embodiment, the present invention provides pure Perfluorohexyloctane of Formula I using column chromatography, preparative HPLC chromatography, crystallization, extraction, evaporation or fractional distillation.

In preferred embodiment, the present invention provides pure Perfluorohexyloctane of Formula I using extraction, evaporation or distillation.

In another embodiment, the stationary (solid) phase used in the column chromatography is selected from silica or alumina.

In another embodiment, the mobile phase (eluent) used in the chromatography is selected from dichloromethane, methanol, acetonitrile, n-hexane, cyclohexane, n-heptane, cycloheptane, ethyl acetate, tetrahydrofuran, water or mixture thereof.

In another embodiment, the present invention provides pure Perfluorohexyloctane of Formula I using crystallization in one or more suitable solvents.

In another embodiment, the one or more solvents used in the present invention for preparation & purification of compound of Formula I and its intermediates are selected from methanol, ethanol, 1-propanol, 2-propanol, n-butanol, isobutanol, nitromethane, chloroform, acetonitrile, acetone, MIBK, MEK, ethyl acetate, propyl acetate, n-pentyl acetate, isopropyl acetate, butyl acetate, propionitrile, diethylether, dimethylether, diisopropylether, diphenylether, MTBE, tetrahydrofuran, methyl tetrahydrofuran, 1,4-dioxane, dimethoxyethane, o-xylene, m-xylene, p-xylene, n-pentane, cyclopentane, n-hexane, n-heptane, cyclohexane, cycloheptane, benzene, toluene, xylene, dichloromethane, dichloroethane, tetrachloromethane, chlorobenzene, dimethyl acetamide (DMA), dimethylformamide (DMF), water or like.

In another embodiment, the reducing agent used for the preparation of compound of Formula I from compound of Formula II is selected from, but not limited to, Zn/HCl/ acetic acid or Pd/C/H2, Tributyltin hydride, LiAlH4/ NaBH4, Ni, or Raney Nickel.

In another embodiment, reduction of compound of formula II is carried out in the range of 10 to 90°C.

In another embodiment, reduction of compound of formula II is carried out in the presence of reducing agent and suitable acid.

In another particular embodiment, the compound of Formula I is prepared as per the Scheme 1 as mentioned below:
Scheme 1:-

In another particular embodiment, the compound of Formula I is prepared as per the Scheme 2 as mentioned below:

Scheme 2:-

In another embodiment, base used for preparing compound of Formula I are selected from the group comprising of, but not limited to alkali metal or alkaline earth metal hydride, hydroxide, bicarbonate, carbonate for example sodium hydride, sodium hydroxide, sodium bicarbonate, sodium carbonate, lithium hydroxide, potassium hydroxide, potassium bicarbonate, potassium carbonate, caesium hydroxide, caesium carbonate, magnesium carbonate, magnesium hydroxide, ammonia gas, liquid ammonia, ammonium hydroxide, alkyl amines such as methylamine, ethylamine, dimethylamine, diethylamine, diisopropylamine, triethylamine, trimethylamine, DIPEA (N,N-Diisopropylethylamine); and the like.

In the preferred embodiment, base used for the preparation of compound of Formula I are selected from the group comprising of, ammonia gas, liquid ammonia, ammonium hydroxide, alkyl amines such as methylamine, ethylamine, dimethylamine, diethylamine, diisopropylamine, triethylamine, trimethylamine, N,N-Diisopropylethylamine (DIPEA), sodium hydroxide, sodium bicarbonate, sodium carbonate, lithium hydroxide, potassium hydroxide, potassium bicarbonate, potassium carbonate or mixture thereof.

In another embodiment, the base used for preparation of compound of Formula I in the range of 10:1 to 1:10 of compound of Formula II.

In another embodiment, the present invention provides substantially pure of Perfluorohexyloctane, compound of Formula I.

In another embodiment, the compound of Formula I of the present invention characterized by chemical purity of at least 95%, preferably at least 98%, more preferably at least 99% and most preferably at least 99.9% as measured by HPLC.

In further embodiment, the present invention provides Perfluorohexyloctane having purity 99.5% and above, and preferably 99.9% and above by HPLC.

In another embodiment, the present invention provides pure Perfluorohexyloctane (CF3(CF2)5(CH2)7CH3) which is free from other impurities.

In another embodiment, the present invention provides pure Perfluorohexyloctane (CF3(CF2)5(CH2)7CH3) which is free from other isomers.

In another embodiment, the present invention provides pure Perfluorohexyloctane (CF3(CF2)5(CH2)7CH3) which is free from CF3-(CF2)5-CH(CH3)-(CH2)5-CH3.

In another embodiment, process of preparation of compound of Formula I is performed in situ without isolation of intermediates.

In another embodiment, the present invention provides substantially pure compound of Formula I, substantially free from impurities wherein each impurity is less than about 0.2% v/v.

Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.

EXAMPLES
Example 1: Synthesis of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodotetradecane (Formula II):
Charged 200g of perfluorohexyl iodide followed by addition of 52.84 g of 1-octene to round bottom flask at room temperature. AIBN was added to the round bottom flask at 25 to 40°C temperature. Temperature was raised upto 70 to 110°C and reaction mass was maintained for 3.0 to 10.0 hrs. After completion of the reaction, reaction mass was distilled out under vacuum at 60 to 85°C. Compound of Formula II was obtained as a degassed oily mass product (207.0g, 83%yield); Purity 97.09% by GC.

Example 2: Synthesis of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodotetradecane (Formula II):
Charged 300g of perfluorohexyl iodide, AIBN to the round bottom flask at 25 to 40°C. Heated the reaction mass and added 83.03 g of 1-octene at 50 to 100°C to round bottom flask. Stirred the mass at 70 to 110°C and reaction mass was maintained for 2.0 to 10.0 hrs. After completion of the reaction, reaction mass was distilled out under high vacuum at 60 to 85°C. Compound of Formula II was obtained as a degassed oily mass product (370.0g, 97.62%yield); Purity 91.38% by GC.

Example 3: Preparation of Compound of Formula IIa:
Charged compound of Formula II (10.0g) as obtained from example 1 followed by addition of sodium hydroxide (2.15g) and methanol (60.0 mL) to round bottom flask at room temperature to get reaction mass. Heated the reaction mass to 45 to 50°C for 6.0 to 8.0hrs. After completion of reaction distilled solvent and Extract material with di isopropyl ether at 25 to 30°C. Distilled out the solvent completely under vacuum at 40°C to yield compound of Formula IIa (6.50g, 84.4% yield); Purity is 96.06% by GC.

Example 4: Preparation of Compound of Formula IIa:
Charged methanol (500ml) and NaOH flakes (28.70g) at room temperature to get reaction mass and followed by the addition of compound of Formula II (120.0g) as obtained from example 1 to round bottom flask. Maintained the reaction mass to 20 to 50°C for 1.0 to 8.0hrs. After completion of reaction, distilled out solvent and workup with n-heptane and water at 25 to 40°C. Distilled out the solvent completely under vacuum at 40°C to yield compound of Formula IIa (81.60g, 83.31% yield); Purity is 92% by GC.

Example 5: Synthesis of Perfluorohexyloctane (Formula I):
Charged compound of formula II (10.0g) as obtained in example 1 followed by the addition of 100ml ethanol, 3.50g DIPEA and 10% Pd/C (1.0g) into a reactor. 4 to 6 kg/cm3 H2 pressure was applied, temperature was raised up to 60 to 75°C. Reaction mass was maintained for 18 to 30hrs at 60 to 75°C and 2 to 8 Kg/cm2 of H2 pressure. After completion of reaction, reaction mass was filtered through celite and washed with ethanol. Filtrate was collected and distilled at 40 to 55°C under vacuum. Charged 30ml of n-heptane to above distilled material at 25 to 30°C and mixture was stirred, settled and separated the layers. Upper layer (organic layer) was collected and lower layer was extracted two times with n-heptane. Combined all the organic layers, washed with 30ml DM water distilled at 30 to 55°C. Compound of formula I obtained as a degassed oily mass product (4.28g, 56.0% yield); Purity is 94.0% by GC.

Example 6: Synthesis of Perfluorohexyloctane (Formula I):
Charged compound of formula II (150.0g) as obtained in example 1 followed by the addition of 600 ml of ethanol into RBF. Charged zinc powder (35.14g) to the reaction mass. Added acetic acid solution (75ml in 150ml ethanol) slowly at 25to 60°C to the reaction mass. Maintained the reaction mass for 1 to 8hrs at 25 to 30°C. Filtered the reaction mass through celite & washed with ethanol. Distilled out the filtrate at 30 to 55°C. Charged DM water (300ml) & diisopropyl ether (450ml) into above distilled mass. Stirred, settled & separated the layers. Extracted aqueous layer with diisopropyl ether (150ml). Combined all the organic layers & washed with DM water (300ml). Distilled the organic layer at 30 to 55°C to get compound I as a degassed oily mass (96.0g, 83.0% yield); Purity is 71.3% by GC.

Example 7: Synthesis of Perfluorohexyloctane (Formula I):
Charged compound of Formula IIa (10.0g) followed by addition of 1.0 g of Palladium carbon (10.0%) and methanol 100.0 ml to autoclave (Pressure reactor) at room temperature. Heated mass at 30 to35°C for 8 to 12.0 hrs. After reaction completion filter catalyst and distilled out solvent under vacuum. Extract product with di isopropyl ether. Distilled out solvent completely under vacuum at 40°C to get compound of Formula I (6.48g, 65.0% yield); Purity is 96.84% by GC.

Example 8: Synthesis of Perfluorohexyloctane (Formula I):
Charged compound of Formula IIa (19.50g) followed by addition of 3.0 g of palladium carbon and 100.0 ml of methanol to autoclave (Pressure reactor) at room temperature. Heated the reaction mass at 30 to 35°C for 8 to 12.0 hrs under hydrogen pressure (2-10 kg/cm2). After reaction completion, filtered catalyst and distilled out solvent under vacuum and performed workup with n-heptane and water. Distilled out solvent completely under vacuum at 40°C to get compound of Formula I (15.0g, 76.92% yield); Purity is 87.14% by GC.

Example 9: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (2.0g) as obtained in example 5 followed by the addition of 10ml methanol, into RBF. Reaction mass was maintained for 40 to 60 minutes at 25 to 35°C. Reaction mass was filtered through celite and washed with 2.0 ml methanol. Filtrate was collected and distilled at 40 to 55°C under vacuum. Pure compound of formula I obtained as a degassed oily mass product (1.80g, 90.0 % yield), purity is 97.87 % by GC.

Example 10: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (47.0g) as obtained in example 5. Fractional distillation of oily mass at 60 to 90 °C under high vacuum to give pure compound of formula I obtained as an oily mass product (22.0g, 46.80 % yield), purity is 97.88 % by GC.

Example 11: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (5.0g) as obtained in example 5 followed by the addition of 15ml methanol, into RBF. Reaction mass was maintained for 15 to 20 minutes at 45 to 50°C. Reaction mass cooled to -30 to -40°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 2.0 ml methanol. Pure compound of formula I obtained as an oily mass product (2.80g, 56.0% yield), purity is 98.02% by GC.

Example 12: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (2.0g) as obtained in example 5 followed by the addition of 20ml n-Heptane, into RBF. Reaction mass was cooled to -30 to -40°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 2.0 ml n-heptane. Pure compound of formula I obtained as an oily mass product (0.60g, 30.0%yield), purity is 99.55% by GC.

Example 13: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (2.0g) as obtained in example 5 followed by the addition of 20ml Diisopropyl ether into RBF. Reaction mass was cooled to -30 to -40°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 2.0 ml Diisopropyl ether. Pure compound of formula I obtained as an oily mass product (0.65g, 32.50% yield), purity is 99.77% by GC.

Example 14: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (15.0g) followed by the addition of 293ml of acetone into RBF. Reaction mass was cooled to -30 to -70°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 30ml of acetone. Pure compound of formula I obtained as an oily mass product (10.0g, 51% yield), purity is 99.91% by GC.

Example 15: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (15.0g) followed by the addition of 293ml of acetone into RBF. Reaction mass was cooled to -30 to -70°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 30ml of acetone. It is dissolved in 30.0 ml of isopropanol at NMT 60°C and filtered through micron filter. Distilled out solvent under vacuum at NMT 70°C. Pure compound of formula I obtained as an oily mass product (10.0g, 51% yield), purity is 99.90% by GC.
Example 16: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (15.0g) followed by the addition of 293ml of acetone into RBF. Reaction mass was cooled to -30 to -70°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 30ml of acetone. Compound dissolved in 30 ml of ethanol at NMT 60°C and filtered through micron filter. Distilled out solvent under vacuum at NMT 70°C. Pure compound of formula I obtained as an oily mass product (10.0g, 51% yield), purity is 99.92% by GC.

Example 17: Purification of Perfluorohexyloctane (Formula I):
Charged compound of formula I (15.0g) followed by the addition of 293ml of acetone into RBF. Reaction mass was cooled to -30 to -70°C & maintained for 1.0hr. Reaction mass was filtered and washed with chilled 30ml of acetone. Compound dissolved in 30 ml of acetone at NMT 60°C and filterd through micron filter. Distilled out solvent under vacuum at NMT 60°C. Pure compound of formula I obtained as an oily mass product (10.0g, 51% yield), purity is 99.90% by GC.
,CLAIMS:We claim:
1. A process for the preparation of compound of formula I, comprising

a) reacting perfluorohexyl iodide of formula III,

with compound of Formula IV,

in the presence of a solvent to give an intermediate compound of formula II; and

b1) reducing compound of Formula II get compound of Formula I;
or
b2) converting the compound of Formula II to compound of Formula IIa in the presence of a base; and
;
reducing the compound of Formula IIa to get compound of Formula I.

2. The process as claimed in claim 1, wherein the reduction is carried out in the presence of a reducing agent selected from, Zn/HCl/acetic acid, Pd/C/H2, tributyltin hydride, LiAlH4/ NaBH4, nickel and Raney nickel and base used in step b2 selected from sodium hydroxide, potassium hydroxide and lithium hydroxide.

3. The process as claimed in claim 1, wherein the solvent is selected from methanol, ethanol, n-propanol, isopropanol or mixtures thereof

4. The process as claimed in claim 1, wherein the reduction is carried out optionally in the presence of a base selected from the group comprising of, ammonia gas, liquid ammonia, ammonium hydroxide, alkyl amines such as methylamine, ethylamine, dimethylamine, diethylamine, diisopropylamine, triethylamine, trimethylamine, N,N-Diisopropylethylamine (DIPEA), sodium hydroxide, sodium bicarbonate, sodium carbonate, lithium hydroxide, potassium hydroxide, potassium bicarbonate, potassium carbonate or mixture thereof.

5. A process for the purification of compound of formula I, comprising steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) optionally, heating the reaction mass;
c) optionally, cooling the reaction mass; and
d) isolating pure compound of Formula I.

6. A process for the purification of compound of formula I, comprising steps of:
a) adding one or more suitable solvent to the compound of Formula I to get reaction mass;
b) cooling the reaction mass;
c) filtering the reaction mass to obtain residue;
d) adding one or more suitable solvent to the residue;
e) heating the reaction mass; and
f) isolating pure compound of Formula I.

7. The process as claimed in claim 5 or 6, wherein the solvent is selected from methanol, ethanol, isopropanol, n-propanol, acetone, n-heptane, n-pentane, tetrahydrofuran, dimethyl ether, diethyl ether, diisopropyl ether, dioxane and water or mixture thereof.

8. The process as claimed in claim 5 or 6, wherein the heating temperature is between 25 to 100 °C and cooling temperature is between -20 to -80 °C.

9. The process as claimed in claim 1, 5 or 7, wherein Perfluorohexyloctane (CF3(CF2)5(CH2)7CH3) is free from CF3-(CF2)5-CH(CH3)-(CH2)5-CH3.

10. The process as claimed in claim 1, 5 or 7, wherein Perfluorohexyloctane having purity of 97% and above by GC.

Dated 17th Day of January, 2025 For Mankind Pharma Ltd.

Dr. Anil Kumar
Chief Scientific Office