DESC:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULE, 2003
(Section 10 and Rule 13)

COMPLETE SPECIFICATION

“A PROCESS FOR THE PREPARATION OF AMINOCAPROIC ACID”

AMNEAL PHARMACEUTICALS COMPANY GmbH
a Swiss Company having its office at
Turmstrasse 30,
6312 Steinhausen,
Switzerland.

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 preparation of aminocaproic acid (I).
BACKGROUND OF INVENTION
Aminocaproic acid is useful in enhancing hemostasis when fibrinolysis contributes to bleeding. Aminocaproic acid is also known by chemical name of 6-aminohexanoic acid. It is marketed in the United States of America by Clover Pharmaceuticals under the trade name Amicar® and represented by following structure:

Aminocaproic acid has pharmaceutical use as well as non-pharmaceutical use in polymer industry to prepare nylon. Processes for the preparation of non-pharmaceutical grade 6-aminocaproic acid are extensively reported in literature, however, getting pharmaceutical grade 6-aminocaproic acid with low ash content, low heavy metal content and in high purity is challenging.
Organic Syntheses, Coll. Vol. 4, p.39 (1963); Vol. 32, p.13 (1952) describes hydrolysis of e-caprolactam using concentrated hydrochloric acid to get e-aminocaproic acid hydrochloride and further conversion into e-aminocaproic acid by means of a column containing Amberlite IR-4B resin. Resin based ion exchange chromatography is expensive and not suitable for large scale production.
US3655748 discloses preparation of 6-aminocaproic acid with low ash content by hydrolysis of e-caprolactam in presence of barium hydroxide. At the end of the reaction, the solution is neutralized by adding CO2 and the formed barium carbonate precipitate is filtered off to obtain free acid of 6-aminocaproic acid. Barium carbonate is toxic and not preferred for the preparation of active pharmaceutical ingredient.
US8809581 discloses a process wherein the hydrolyzed caprolactam is reacted with a solubility regulating agent to form an aminocaproic acid intermediate that has reduced water solubility, to remove undesired salts formed during reaction by water washing and 6-aminocaproic acid (with low ash content) is obtained after hydrogenation using Pd catalyst. Process involves use of additional protection and deprotection step adding to the cost of development. Further, it involves use of heavy metal catalyst and maintaining heavy metal below limits would lead to yield loss.
6-aminocaproic acid is highly water soluble and getting 6-aminocaproic acid with minimal inorganic salt impurity generated during neutralization of 6-aminocaproic acid HCl salt is challenging. US9776953 addressed this problem by using organic base for neutralization of 6-aminocaproic acid HCl salt in methanol, wherein 6-aminocaproic acid is insoluble in methanol and organic salt impurity generated during neutralization is soluble in methanol. Selective solubility in methanol helps in getting 6-aminocaproic acid with high purity. However, 6-aminocaproic acid is amphoteric in nature and for neutralization exact pH is advisable. As neutralization with organic base is carried out in non-aqueous medium, where pH measurement is not feasible, variable yield would be obtained during neutralization if pH is lower or higher than isoelectric point.
There is still the need to have a more suitable alternative method for isolating and purifying 6-aminocaproic acid (I).
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an illustration of a powder X-ray diffraction (PXRD) pattern of Form-AM of 6-aminocaproic acid.
SUMMARY OF THE INVENTION
The present invention relates to 6-aminocaproic acid, which is prepared in high purity and high yield.
In an aspect, the present invention provides a process for the preparation of pure 6-aminocaproic acid (I),

which comprises:
a) ring opening of caprolactam (III) to form a compound of formula IV;

b) converting the compound of formula IV into crude 6-aminocaproic acid (I) using an inorganic base or an acid;
c) solubilizing crude 6-aminocaproic acid (I) in a solvent;
d) crystallizing pure 6-aminocaproic acid by adding anti-solvent to the solution of step (c); and
e) isolating pure 6-aminocaproic acid (I).
In another aspect, the present invention provides a process for the purification of crude 6-aminocaproic acid (I), which comprises:

a) solubilizing crude 6-aminocaproic acid (I) in a solvent;
b) crystallizing pure 6-amino by adding anti-solvent to the solution of step (a); and
c) isolating pure 6-aminocaproic acid (I).
In yet another aspect, the present invention provides a crystalline form of 6-aminocaproic acid, designated as Form AM.
DETAIL DESCRIPTION OF INVENTION
All percentages and ratios used herein are by weight of the total composition and all measurements made are at about 25°C and about normal pressure, unless the context requires otherwise. All temperatures are in degree Celsius unless specified otherwise. As used herein, “comprising” or “comprises” (open-ended) means the element or elements recited, or their equivalents in structure or function, plus any other element or elements which are not recited. The terms “having” and “including” are also to be construed as open-ended. All ranges recited herein include the endpoints, including those that recite a range “between” two values. Whether so indicated or not, all values recited herein are approximate as defined by the circumstances, including the degree of expected experimental error, technique error, and instrument error for a given technique used to measure a value. Unless defined otherwise, technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art.
The term "about" when used in the present invention preceding a number and referring to it, is meant to designate any value which lies within the range of ±10%, preferably within a range of ±5%, more preferably within a range of ±2%, still more preferably within a range of ±1 % of its value. For example "about 10" should be construed as meaning within the range of 9 to 1 1 , preferably within the range of 9.5 to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably within the range of 9.9 to 10.1 .
The word “pure” as used herein means that 6-aminocaproic acid has sulphated ash content of not greater than 2 wt%. Sulphated ash is the total weight percent of residue remaining after a compound has been carbonised, and the residue subsequently treated with sulphuric acid and heated to constant weight.
“Room temperature” as used herein refers to the temperature as understood by one skilled in the art to be in range of about 20°C to about 30°C.
Optionally, in carrying out the processes according to the present invention, the reaction product of a given step can be carried forward to the next step without the isolation of the product or with isolation but without purifying the product, that is, one or more reactions in a given process can be carried out in-situ as one pot process optionally in the presence of the same reagent/s used in a previous step wherever appropriate to do so, to make the process of the present invention economical and commercially more viable.
Unless otherwise indicated, the solid state forms of the present invention may be dried. Drying may be carried out using methods and equipments as known by one skilled in the art such in a tray dryer, vacuum oven, Buchi® Rotavapor®, air oven, fluidized bed dryer, spin flash dryer, flash dryer, cone dryer, agitated nutsche filter cum dryer, nauta dryer or the like or any other suitable dryer.
The drying may be carried out at a temperature between about -20°C to about 150°C.The drying may be carried out under reduced atmospheric pressure, that is, less than standard atmospheric pressure or at atmospheric pressure or any other suitable pressure. The drying may take place over a period of about 30 minutes to about 12 hours.The dried product may be subjected to techniques such as sieving to get rid of lumps before and/or after drying. The dried product may be optionally milled to get a desired particle size. Milling or micronization may be performed before drying and/or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer mills, and jet mills.
In an embodiment, 6-aminocaproic acid of present invention has average particle size of particles between 1 to 100 µm, less than 90 µm, less than 80 µm, less than 60 µm, less than 50 µm, less than 40 µm, less than 30 µm, less than 20 µm, less than 10 µm, less than 5 µm or any other suitable particle sizes. In another embodiment, of 6-aminocaproic acid of present invention may have particle size distribution: D10 of particles smaller than 20 µm, smaller than 15 µm, smaller than 10 µm, or smaller than 5 µm; D50 of particles smaller than 100 µm, smaller than 90 µm, smaller than 80 µm, smaller than 70 µm, smaller than 60 µm, smaller than 50 µm, smaller than 40 µm, smaller than 30 µm, smaller than 20 µm, smaller than 10 µm; D90 of particles smaller than 200 µm, smaller than 175 µm, smaller than 150 µm, smaller than 140 µm, smaller than 130 µm, smaller than 120 µm, smaller than 110 µm, smaller than 100 µm, smaller than 90 µm, smaller than 80 µm, smaller than 70 µm, smaller than 60 µm, smaller than 50 µm, smaller than 40 µm, smaller than 30 µm, smaller than 20 µm, smaller than 10 µm. Particle size distributions of of 6-aminocaproic acid particles may be measured using any techniques known in the art. For example, particle size distributions of of 6-aminocaproic acid particles may be measured using microscopy or light scattering equipment, such as, for example, a Malvern Master Size 2000 from Malvern Instruments Limited, Malvern, Worcestershire, United Kingdom. As referred herein, the term “D10” in the context of the present invention is 10% of the particles by volume are smaller than the D10 value and 90% particles by volume are larger than the D10 value. “D50” in the context of the present invention is 50% of the particles by volume are smaller than the D50 value and 50% particles by volume are larger than the D50 value. “D90” in the context of the present invention is 90% of the particles by volume are smaller than the D90 value and 10% particles by volume are larger than the D90 value.
For XRD, the relative intensities of the peaks can vary, depending upon the sample preparation technique, the sample mounting procedure and the particular instrument employed. Moreover, instrument variation and other factors can often affect the 2- theta values. Therefore, the peak assignments of diffraction patterns can vary by plus or minus about 0.2°.
PXRD data reported herein are obtained using a PANalytical X-ray Diffractometer, using copper Ka radiation wavelength 1.5418A.
The inventors of the present invention have surprisingly found that pure 6-aminocaproic acid (I) can be obtained by dissolving crude 6-aminocaproic acid into solvent followed by addition of anti-solvent wherein inorganic impurities would have solubility in solvent and pure 6-aminocaproic acid would precipitate out.
The present invention provides a process for the preparation of pure 6-aminocaproic acid (I),

which comprises:
a) ring opening of caprolactam (III) to form a compound of formula IV;

b) converting compound of formula IV into crude 6-aminocaproic acid (I) using an inorganic base or an acid;
c) solubilizing crude 6-aminocaproic acid (I) in a solvent;
d) crystallizing pure 6-aminocaproic acid (I) by adding anti-solvent to the solution of step (c); and
e) isolating pure 6-aminocaproic acid (I).
In step a), ring opening of caprolactam (III) to form a compound of formula IV can be performed in presence of an acid or a base and a solvent. The base used can be inorganic base. Inorganic base used includes but are not limited to hydroxide, carbonate of alkali and alkaline earth metals such as sodium carbonate, sodium hydroxide, potassium carbonate, potassium hydroxide, lithium carbonate, lithium hydroxide, cesium carbonate, and the like. The acid used can be mineral acid or organic acid. Mineral acid used includes but not limited to sulfuric acid, phosphoric acid and a hydrohalic acid, preferably hydrochloric acid. An organic acid used includes but not limited to sulfonic acid, typically camphorsulfonic acid, p-toluenesulfonic acid, methanesulfonic acid or trifluoromethanesulfonic acid; an aryl carboxylic acid, typically a benzoic acid; a C1-C4 alkyl-carboxylic acid, wherein the C1-C4 alkyl group, which can be straight or branched, optionally substituted by one or more halogen atoms, preferably from one to three chloro or fluoro atoms, typically acetic acid or trifluoroacetic acid.
The solvent used in step a) can be selected from following solvent as single solvent or mixture thereof. Solvent used includes but are not limited to chlorinated hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbon such as toluene, xylene, chlorobenzene, bromobenzene; ether such as dioxan, tetrahydrofuran (THF), methyl tertbutyl ether (MTBE), ethyleneglycol dimethylether, diethyleglycol dimethylether; nitrile such as acetonitrile; ester such as ethylacetate, isopropyl acetate; ketone such as acetone, methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK); polar aprotic such as N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dimethyl acetamide (DMAc), N-methylpyrrolidone (NMP); polar protic such as alcoholic solvent C1-6 linear or branched alcohol such as methanol, ethanol, isopropanol, propanol, butanol and the like; water or mixtures thereof.
The reaction can be conducted over a range of temperatures, e.g., from about -20°C to about 200°C, but is preferably, conducted at a temperature at which the solvent refluxes.
The ratio of equivalents between caprolactam (III) and an acid or a base used for ring opening can range from 1:1 to about 1:10, respectively. Preferably, the ratio of equivalents between caprolactam (III) and an acid or a base used for ring opening can range from 1:1 to about 1:5, more preferably the ratio is from 1:1 to about 1:3.
In an embodiment, optionally in step (a), the reaction product can be carried forward to the next step without the isolation of the product, that is, process can be carried out in-situ as one pot process.
In step b), compound of formula IV is converted into crude 6-aminocaproic acid (I) using an inorganic base or an acid based on the addition salt formed in step (a). The reaction may be carried out in presence of water or alcohol; such as methanol, ethanol, isopropanol, n-butanol, t-butanol, and the like; ketones such as acetone; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; esters such as ethyl acetate, aminos such as triethylamine; amides such as N,N-dimethylformamide, or dimethylacetamide; chlorinated solvents such as dichloromethane and other solvents such as toluene, dimethyl sulfoxide, acetonitrile, and mixtures thereof. Inorganic base used includes but are not limited to hydroxide, carbonate of alkali and alkaline earth metals such as sodium carbonate, sodium hydroxide, potassium carbonate, potassium hydroxide, lithium carbonate, lithium hydroxide, cesium carbonate, and the like. The acid used includes but not limited to sulfuric acid, phosphoric acid and a hydrochloric acid. The amount of an inorganic base or an acid can be in the range of 1 to about 10 equivalents, preferably in range of 1 to about 5 equivalents, based on 1 equivalent of the compound of formula IV.
In step (c), crude 6-aminocaproic acid (I) is solubilized in a solvent. The solvent that may be used includes, but not limited to, ethylene glycol, propylene glycol, glycerine, water, and the like. The dissolution temperatures can range from about -20°C to about reflux temperature of the solvent, depending on the solvent used for dissolution, as long as a clear solution of 6-aminocaproic acid is obtained. The solution can optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable material to remove color and/or to clarify the solution. Optionally, the solution obtained above can be filtered to remove any insoluble particles. The insoluble particles can be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques. The solution can be filtered by passing through paper, glass fiber, or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature crystallization.
In step-(d), pure 6-aminocaproic acid is crystallized by adding anti-solvent to the solution of step (c). The anti-solvent that may be used includes, but not limited to, Dimethylformamide (DMF), Dimethyl sulfoxide (DMSO), N-Methyl-2-pyrrolidone (NMP) and the like. The anti-solvent as used herein refers to a solvent in which 6-aminocaproic acid at the temperature at which the process is performed is less soluble than in the solvent, so that 6-aminocaproic acid crystallizes when it is mixed with the anti-solvent. The solvent used in the dissolution of 6-aminocaproic acid is miscible with anti-solvent. A solvent is miscible with the anti-solvent, if, the temperature at which process is carried out they form a homogenous solvent mixture.
Alternatively, anti-solvent may be added to the solution of 6-aminocaproic acid. When the solution containing 6-aminocarproic acid dissolved in solvent is mixed with anti-solvent, 6-aminocaproic acid precipitates, it is not necessary to wait for a certain amount of time after mixing; however, crystallization may require aging for additional time. Aging is typically done at a temperature of less than about 50°C, or less than about 40°C, or less than about 30°C, or less than about 20°C, or less than about 10°C, or less than about 5°C, or less than about 0°C, or less than about -5°C, or any other suitable temperature. The aging may be typically done for about 24 hours, or about 18 hours, or about 12 hours, or about 10 hours, or about 5 hours, or about 2 hours, or about 1 hour, or any other suitable time period.
In step (e), pure 6-aminocaproic acid (I) is isolated. In an embodiment, 6-aminocaproic acid is precipitated by cooling and the obtained precipitates are isolated. Optionally, isolated precipitates are further dried. 6-aminocaproic acid can be recovered, e.g., by filtration, decantation, centrifugation, gravity filtration, suction filtration or any other techniques for the recovery of the solids. In one of the embodiments, 6-aminocaproic acid can be further recrystallized in order to obtain higher purity.
In another aspect, the present invention provides a process for the purification of crude 6-aminocaproic acid (I), which comprises:

a) solubilizing crude 6-aminocaproic acid (I) in a solvent;
b) crystallizing pure 6-amino by adding anti-solvent to the solution of step (a); and
c) isolating pure 6-aminocaproic acid (I).
In step (a), crude 6-aminocaproic acid (I) is solubilized in a solvent. The solvent that may be used includes, but not limited to, ethylene glycol, propylene glycol, glycerine, water, and the like. The dissolution temperatures can range from about -20°C to about reflux temperature of the solvent, depending on the solvent used for dissolution, as long as a clear solution of 6-aminocaproic acid is obtained. The solution can optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable material to remove color and/or to clarify the solution. Optionally, the solution obtained above can be filtered to remove any insoluble particles. The insoluble particles can be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques. The solution can be filtered by passing through paper, glass fiber, or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature crystallization.
In step-(b), pure 6-aminocaproic acid is crystallized by adding anti-solvent to the solution of step (a). The anti-solvent that may be used includes, but not limited to, Dimethylformamide (DMF), Dimethyl sulfoxide (DMSO), N-Methyl-2-pyrrolidone (NMP) and the like. The anti-solvent as used herein refers to a solvent in which 6-aminocaproic acid at the temperature at which the process is performed is less soluble than in the solvent, so that 6-aminocaproic acid crystallizes when it is mixed with the anti-solvent. The solvent used in the dissolution of 6-aminocaproic acid is miscible with anti-solvent. A solvent is miscible with the anti-solvent, if, the temperature at which process is carried out they form a homogenous solvent mixture.
Alternatively, anti-solvent may be added to the solution of 6-aminocaproic acid. When the solution containing 6-aminocarproic acid dissolved in solvent is mixed with anti-solvent, 6-aminocaproic acid precipitates, it is not necessary to wait for a certain amount of time after mixing; however, crystallization may require aging for additional time. Aging is typically done at a temperature of less than about 50°C, or less than about 40°C, or less than about 30°C, or less than about 20°C, or less than about 10°C, or less than about 5°C, or less than about 0°C, or less than about -5°C, or any other suitable temperature. The aging may be typically done for about 24 hours, or about 18 hours, or about 12 hours, or about 10 hours, or about 5 hours, or about 2 hours, or about 1 hour, or any other suitable time period.
In step (c), pure 6-aminocaproic acid (I) is isolated. In an embodiment, 6-aminocaproic acid is precipitated by cooling and the obtained precipitates are isolated. Optionally, isolated precipitates are further dried. 6-aminocaproic acid can be recovered, e.g., by filtration, decantation, centrifugation, gravity filtration, suction filtration or any other techniques for the recovery of the solids. In one of the embodiments, 6-aminocaproic acid can be further recrystallized in order to obtain higher purity.
In another aspect, the present invention provides a crystalline form of 6-aminocaproic acid, designated as Form AM, characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2T at about 10.62°, 17.70°, 18.43°, 18.62°, 19.19°, 20.10°, 20.61°, 21.31°, 23.30°, 23.94°, 26.16°, 26.78°, 28.34°, 32.19°, 32.28°, 36.92° ± 0.2° 2T.
Figure 1 shows typical X-ray powder diffraction pattern of "Form AM".
The present invention provides a process for the preparation of a crystalline form of 6-aminocaproic acid, designated as Form AM, which comprises:
a) solubilizing 6-aminocaproic acid (I) in mixture of methanol and water;
b) crystallizing pure 6-amino by adding acetone; and
c) isolating Form-AM of 6-aminocaproic acid.
In an embodiment, 6-aminocaproic acid (I) as disclosed in present invention has sulphated ash less 0.1 wt%.
The following examples are given for the purpose of illustrating the present invention and should not be considered as limiting on the scope of the invention.
Example 1 - Preparation of Cyclohexanone oxime (II) from Cyclohexanone:

450 g (4.58 mol) of cyclohexanone and 350 g (5.04 mol) of hydroxyl amine hydrochloride were added in to the methanol at room temperature. The reaction mixture was heated to 60-70°C and maintain for 3 hours at same temperature. Completion of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to 50-55°C and solvent was removed under vacuum below 60°C. Water (350 ml) was added in to the residue and reaction mixture was cooled to 0-10°C. pH was adjusted between 7.0 to 8.0 using 33% aqueous sodium hydroxide solution and stirred for 30 minutes at 25-30°C. Solid compound was filtered under reduced pressure and washed with water (100 ml) to get 480 g of cyclohexanone oxime (I).
Yield: 92.5%
HPLC purity: 99.93%
m/z: 114.2 (M+H), 1H-NMR: (400 MHz, CDCl3) d: 1.65-2.00 (m, 6H), d: 2.44-2.47 (t, 2H), d: 3.18-3.22 (m, 2H), d: 6.48 (s, 1H).
Example 2 - Preparation of Caprolactam (III) from Cyclohexanone oxime (II):

Cyclohexanone oxime (200 g, 1.76 mol) was added (lot wise) to 90% aqueous sulphuric acid solution (600 ml) at 50-60°C, stirred and maintained for 2 hours. Reaction mass was heated to 60-70°C and stirred for 4 hours. Further, reaction mass was heated to 80°C and maintained for 14 hours at same temperature. Completion of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was cooled to 0-5°C, diluted with water (400 ml) and neutralized with 25% aqueous ammonia solution (1475 ml). Mixture was filtered to remove unwanted salt and filtrate was extracted with toluene (2 * 1800 ml). Toluene layers were combined and treated with acidic charcoal (10 g) at 50°C. Toluene was distilled under vacuum below 60°C and cyclohexane (300 ml) was added. The mixture was heated to 45-50°C, stirred and maintained for 30 minutes. Reaction mixture was cooled, filtered under reduced pressure and washed with cyclohexane (100 ml) to get 171.0 g of caprolactam (III).
Yield: 85.5%
HPLC purity: 99.87%
m/z: 114.2 (M+H), 1H-NMR: (400 MHz, CDCl3) d: 1.59-1.69 (m, 6H), d: 2.19-2.22 (t, 2H), d: 2.48-2.51 (t, 2H).
Example 3 - Preparation of pure 6-Aminocproic acid (I) from Caprolactam (III):

A mixture of caprolactam (120 g), conc HCl (120 ml) and water (240 ml) was heated to 98-105°C, stirred and maintained at same temperature for 12-18 hours. The completion of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was cooled to 50-55°C, treated with acidic charcoal (6 g), and filtered the reaction mass. pH of the filtrate was adjusted between 7.0 to 8.0 with 47% aqueous sodium hydroxide solution (120 ml) and distilled under vacuum below 60°C to get crude residue. Methanol (600 ml) and water (36 ml) were added in crude residue and stirred for 2 hours at room temperature. The solid compound was filtered under reduced pressure and washed with methanol (100 ml) to get crude product of 162 gm having HPLC purity: 97.16% and Sulphated Ash: 18.75 wt%.
90 g of above crude product was taken in ethylene glycol (450 ml) and stirred for 1 hour at room temperature to dissolve the product and unwanted salt was removed by filtration. In filtrate, dimethyl sulfoxide (DMSO: 900 ml) was slowly added to precipitate the solid compound and maintained the reaction mixture for 4 hours at room temperature. The solid was filtered under reduced pressure and washed with isopropyl alcohol (90 ml) to get 43.1 g of 6-aminocaproic acid (I) as a white solid.
Yield: 55.7%), HPLC purity: 95.63%, Sulphated Ash: 0.80 wt%.
Example 4 - Preparation of Form-AM of 6-Aminocproic acid (I):
Mixture of 6-Aminocaproic acid (III) (9 g), methanol (45 ml) and water (9 ml) was heated and stirred at 58-65°C for 30 minutes to get clear solution. Reaction mixture was filtered through micron filter paper to remove foreign particles and reaction mixture was cooled to room temperature. Acetone (45 ml) was added slowly to reaction mixture, stirred and maintained for 2 hours. The reaction mixture was filtered under reduced pressure and washed with methanol (9 ml) to get 7.9 gm of 6-Aminocaproic acid (I).
Yield: 87.7%.
HPLC purity: 99.85%, Sulphated Ash: 0.10 wt%
m/z: 132.4 (M+H), 1H-NMR: (400 MHz, D2O) d: 1.19-1.27 (m, 2H), d: 1.41-1.57 (m, 4H), d: 2.03-2.07 (t, 2H), d: 2.83-2.87 (t, 2H).

Dated this 1st day of January 2019

(Signed)________________
Dr. Parva Yogeschandra Purohit
Vice President - IP
,CLAIMS:WE CLAIM:
1. A process for the preparation of pure 6-aminocaproic acid (I),

which comprises:
a) ring opening of caprolactam (III) to form a compound of formula IV;

b) converting the compound of formula IV into crude 6-aminocaproic acid (I) using an inorganic base or an acid;
c) solubilizing crude 6-aminocaproic acid (I) in a solvent;
d) crystallizing pure 6-aminocaproic acid by adding anti-solvent to the solution of step (c); and
e) isolating pure 6-aminocaproic acid (I).
2. The process according to claim 1, wherein step c) involves solubilization of 6-aminocaproic acid in ethylene glycol.
3. The process according to claim 1, wherein step d) involves crystallization of 6-aminocaproic acid by adding dimethyl sulfoxide.
4. A process for the purification of crude 6-aminocaproic acid (I), which comprises:

a) solubilizing crude 6-aminocaproic acid (I) in a solvent;
b) crystallizing pure 6-amino by adding anti-solvent to the solution of step (a); and
c) isolating pure 6-aminocaproic acid (I).
5. The process according to claim 4, wherein step a) involves solubilization of 6-aminocaproic acid in ethylene glycol.
6. The process according to claim 4, wherein step b) involves crystallization of 6-aminocaproic acid by adding dimethyl sulfoxide.
7. A process for the preparation of form-AM of 6-aminocaproic acid (I), which comprises:

a) solubilizing 6-aminocaproic acid (I) in mixture of methanol and water;
b) crystallizing pure 6-amino by adding acetone; and
c) isolating Form-AM of 6-aminocaproic acid.

Dated this 1st day of January 2019
Signature: _______________
Name: Dr. Parva Yogeshchandra Purohit
Vice President - IP