Field of invention:

The present invention relates to an improved process for the preparation of trans- 5-chloro-2,3,3a, 12b-tetrahydro-2-methyl-l H-dibenz[2,3,6,7]oxepino[4,5c]pyrrol-1 -one compound of formula-1.

Formula-1

Trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3,6,7]oxepino [4,5- c]pyrrol-l-one is an important intermediate useful in the preparation of antipsychotic drug asenapine, which is used for the treatment of schizophrenia and acute mania associated with bipolar disorder.

Background of the Invention:

Trans-5-chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7]oxepino [4,5- c]pyrrol-1-one and process for its preparation was disclosed in US 4145434. The disclosed process comprises of reducing 5-chloro-2,3-dihydro-2-methyl-lH-dibenz [2,3:6,7] oxepino[4,5-c]pyrrol-l-one with magnesium in methanol to provide a mixture of 'trans' and 'cis' isomers of 5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3:6,7] oxepino [4,5-c]pyrrol-l-one. The 'trans' isomer is isolated using column chromatography and reacted with lithium aluminium hydride and aluminium chloride to provide asenapine. The said process involves chromatographic separation, hence not suitable for commercial scale up.

EP 1710241 discloses a process which involves the reduction of double bond in ll-chloro-2,3-dihydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one by
treating with magnesium in methanol/toluene solvent to provide a mixture of required 'trans' isomer and the unwanted 'cis' isomer of ll-chloro-2,3,3a,12b-tetrahydro-2- methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one in a ratio of 1:4 respectively. The trans-isomer is separated from the racemic mixture using chromatography over silica gel. The 'cis' isomer obtained after separation is converted into trans-isomer by isomerization using l,5-diazabicyclo[4.3.0]non-5-ene (DBN). But the isomerization is only partial providing a mixture of 'trans' isomer and 'cis' isomer in the ratio of 1:2. The 'trans' isomer from this racemic mixture is once again separated using chromatography over silica gel.

Repeating the cycle multiple times provided overall yield of 38% of the trans- isomer.
The said process involves chromatographic separation in each cycle. The use of chromatographic separation makes the process cumbersome, time consuming, and uneconomical. It also leads to the generation of lot of spent solvents and solid waste which are difficult to dispose which may lead to the pollution of the environment. Hence it becomes imperative to avoid chromatographic separation for the process to be more effective. The process also involves repeated racemization. Therefore in order to avoid it there is a need for 'cis' isomer to be converted more effectively into trans-isomer.

Hence there is a need for a process for the preparation which can reliably be carried out in an industrial scale, in a convenient and cost efficient manner. And also the process should be more eco-friendly.

The present invention overcomes the problems of the above mentioned prior art.

Advantages of the Present Invention:

• Provides an improved process for the preparation of trans-5-chloro-2,3,3a,12b- tetrahydro-2-methyl-1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one with high yield and purity.

• Avoids chromatographic separation hence conducive to be carried out in large scale process.

• Eco-friendly and cost effective process.

Brief description of the invention:

The present invention is to provide an improved process for the preparation of trans-5-chloro-2,3,3a, 12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] [4,5-c] pyrrol-1 -one compound of formula-1.

The first aspect of the present invention is to provide an improved process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c]pyrrol-l-one compound of formula-1, which comprises of,

a) Suspending a mixture of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one compound of formula-2 and 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU) in a suitable inert solvent, and heating the reaction mixture at a suitable temperature for a suitable period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to high temperature to get a clear solution,

d) lowering the temperature of the solution, preferably to about 50°-60°C, more preferably to 50°- 55°C to precipitate a solid,

e) filtering off the solid obtained and collecting the filtrate,

f) distilling off the solvent from the filtrate obtained in step-e), to provide trans-5- chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l- one compound of formula-1.

The second aspect of the present invention is to provide a process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c] pyrrol-l-one compound of formula-1, which comprises of,

a) Suspending a mixture of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2 and 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU) in a suitable inert solvent, and heating the mixture to higher temperature for a period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to higher temperature,

d) filtering the suspension and collecting the filtrate,

e) distilling off the solvent from the filtrate obtained in step-d), to provide trans-5- chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l- one compound of formula-1.

The third aspect of the present invention is to provide a process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c] pyrrol-1-one compound of formula-1, which comprises of,

a) Suspending a mixture of cis and trans isomers of 5-chloro-2,3,3a,12b-tetrahydro- 2-methyl-1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one in isopropyl alcohol,

b) heating the suspension to higher temperature,

c) filtering the suspension and collecting the filtrate,

d) distilling off the solvent from the filtrate obtained in step-c) to provide trans-5- chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l- one compound of formula-1.

The fourth aspect of the present invention is to provide a process for the preparation of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c]pyrrol-l-one compound of formula-2, which comprises of,

a) Reacting 5-Chloro-2,3-dihydro-2-methyl-1 H-dibenz[2,3:6,7]oxepino[4,5-c] pyrrol-1-one compound of formula-3 with magnesium in presence of catalytic amount of iodine in methanol,

b) concentrating the solvent from the mixture obtained in step-a) and adding appropriate amount of isopropyl alcohol to the concentrate to precipitate cis-5- chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7] oxepino[4,5-c]pyrrol- 1-one compound of formula-2 as a solid,

c) filtering the mixture to isolate the solid and optionally recrystallizing it using isopropyl alcohol to provide pure cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl- 1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2.

Detailed description of the invention

The present invention is to provide an improved process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c] pyrrol- 1-one compound of formula-1.

Throughout this disclosure, compounds represented by structural formulae having a pair of bold and hashed wedged bonds as shown, e.g., in compound of formula-1 or a pair of bold wedged bonds as shown, e.g., in compound of formula-2, refer to "trans" or "cis" diastereoisomers respectively. Each of the compounds may exist as a single enantiomer having the absolute stereo chemical configuration indicated by the wedged bonds, or having the opposite absolute configuration or as a mixture of enantiomers having the relative stereo chemical configuration indicated by the wedged bonds.

The suitable solvents, wherever necessary, used in the present invention are selected from "hydrocarbon solvents" like toluene, hexane, heptane and cyclohexane; "chloro solvents" like dichloromethane, dichloroethane, carbon tetrachloride and chloroform.

The first aspect of the present invention is to provide an improved process for the preparation of trans-5-chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7]oxepino [4,5-c]pyrrol-l-one compound of formula-1, which comprises of,

Formula-1
a) Suspending a mixture of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2,

Formula-2 and l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in a suitable inert solvent, and heating the reaction mixture at a suitable temperature for a suitable period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to high temperature to get a clear solution,

d) lowering the temperature of the solution, preferably to about 50°-60°C, more preferably to 50°- 55°C to precipitate a solid,

e) filtering off the solid obtained and collecting the filtrate,

f) distilling off the solvent from the filtrate obtained in step-e), to provide trans-5- chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-

1- one compound of formula-2.

The cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino [4,5- c]pyrrol-l-one compound of formula-2, used as the input in the present invention was prepared according to the process similar to the process disclosed in US 4145434.
The second aspect of the present invention is to provide a process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c]pyrrol-l-one compound of formula-1, which comprises of,

a) Suspending a mixture of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2 and 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU) in a suitable inert solvent, and heating the mixture to higher temperature for a period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to higher temperature,

d) filtering the suspension and collecting the filtrate,

e) distilling off the solvent from the filtrate obtained in step-d), to provide trans-5- chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l- one compound of formula-1.

The third aspect of the present invention is to provide a process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c] pyrrol-1-one compound of formula-1, which comprises of,

a) Suspending a mixture of cis and trans isomers of 5-chloro-2,3,3a,12b-tetrahydro-
methyl-1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one in a isopropyl alcohol,

b) heating the suspension to higher temperature,

c) filtering the suspension and collecting the filtrate,

d) distilling off the solvent from the filtrate obtained in step-c, to provide trans-5- chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-1 - one compound of formula-1.

The fourth aspect of the present invention is to provide a process for the preparation of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino [4,5-c]pyrrol-l-one compound of formula-2, which comprises of,

a) Reacting 5-chloro-2,3-dihydro-2-methyl-1 H-dibenz[2,3:6,7]oxepino[4,5-c] pyrrol-l-one compound of formula-3,

Formula-3 with magnesium in presence of catalytic amount of iodine in methanol,

b) heating the reaction mixture to reflux temperature and cool the reaction mixture and quench the reaction mixture with water,

c) adding ethyl acetate to the reaction mixture and stirred.

d) concentrating the organic layer obtained in step-c) and adding appropriate amount of isopropyl alcohol and concentrate to obtain cis-5-chloro-2,3,3a,12b- tetrahydro-2-methyl-lH-dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one compound of formula-2 as a solid,

e) filtering the mixture to isolate the solid and optionally recrystallizing it using isopropyl alcohol to provide pure cis-5-chloro-2,3,3a,12b-tetrahydro-2methyl- 1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2.

EP 1710241 discloses a process which involves the reduction of double bond in 11 -chloro-2,3-dihydro-2-methyl-1 H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-1 -one by
treating with magnesium/ in methanol/toluene solvent to provide a mixture of required 'trans' isomer and the unwanted 'cis' isomer of ll-chloro-2,3,3a,12b-tetrahydro-2- methyl-1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one in a ratio of 1:4 respectively. The trans and cis isomers are separated from the racemic mixture using chromatography over silica gel.
In the present invention the reduction of 5-chloro-2,3-dihydro-2-methyl-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-3 is carried out using 5- 8 equivalents of magnesium/^ in methanol providing a mixture 'trans' and 'cis' isomers of 5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz [2,3,6,7] oxepino [4,5-c]pyrrol-l- one in a ratio of around 2:8. The present invention provides a process in which the pure cis isomer is isolated as pure solid without the use of column chromatography.

The above aspects of the present invention can be practiced using the 11-chloro- 2,3-dihydro-2-methyl-lH-dibenz[2,3:6,7] oxepino [4,5-c] pyrrol-l-one compound of formula-4, as an input material to prepare 'cis' isomer of ll-chloro-2,3,3a,12b- tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-5 and 'trans' isomer of ll-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c] pyrrol-l-one compound of formula-6.

The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.

Examples:

Example-l: Preparation of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c|pyrrol-l-one (formula-2).

To a mixture of magnesium(19.5 grams) and iodine (0.8 grams) in 1000 ml of methanol added 5-chloro-2,3-dihydro-2-methyl-lH-dibenz [2,3:6,7] oxepino [4,5- c]pyrrol-l-one (40 grams) at 25-30°C and stirred the reaction mixture for 30 minutes at 25-30°C. Heated the reaction mixture to reflux temperature and stirred for 1 hour at reflux. After completion of the reaction, the reaction mixture was cooled to 25-30°C and water (400 ml) was added. Adjusted the pH of the reaction mixture to 6.5 by using 20% dil.HC1 at 10-15°C. Ethyl acetate (600 ml) was added to the reaction mixture and stirred for 30 minutes. Both the organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed with 10% NaC1 solution. Distilled off the solvent completely under reduced pressure. 120 ml of isopropyl alcohol was added to the obtained residue and the reaction mixture was cooled to 0-5°C. Stirred the reaction mixture for 2 hrs at 0-5°C. Filtered the obtained solid, washed with isopropyl alcohol and dried to get the title compound. Yield: 20 grams; Melting Point: 148-151°C.

Example-2: Preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one (formula-1).

To a solution of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz [2,3,6,7]oxepino[4,5-c]pyrrol-l-one (15 grams) in toluene (225 ml) added DBU (3.8 grams) at 15-20°C. The reaction mixture temperature was raised to 25-30°C and stirred for 12 hrs. Water (150 ml) was added to the reaction mixture followed by the addition of acetic acid (5 ml). Stirred the reaction mixture for 10 minutes. Both the organic and aqueous layers were separated and the aqueous layer was extracted with toluene (45 ml). Distilled off the solvent completely under reduced pressure. Isopropyl alcohol (45 ml) was added to the obtained residue and heated to reflux temperature. The reaction mixture was cooled to 50-55°C and unwanted precipitate was removed by filtration. Distilled off the solvent completely from filtrate under reduced pressure to get the title compound (trans - isomer).

Yield: 7.3 grams: Melting Point: 140-143°C.

Example-3: Preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3)6,7] oxepino[4,5-c]pyrrol-l-one (formula-1).

To a solution of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz [2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2 (15 grams) in toluene (225 ml) added DBU (3.8 grams) at 15-20°C. The reaction mixture was raised to 25-30°C and stirred for 10-12 hours. Distilled off the solvent completely under reduced pressure to get the residue which contains mixture of cis and trans-isomers. Isopropyl alcohol (45 ml) was added to the obtained residue and heated to reflux temperature. The reaction mixture was cooled to 50-55°C and unwanted precipitate was removed by filtration. Distilled off the solvent completely from filtrate under reduced pressure to get the title compound (trans - isomer). Yield: 7.1 grams.

Example-4: Preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one (formula-1).

The solution of mixture of cis and trans isomers of 5-chloro-2,3,3a,12b- tetrahydro-2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one (15 grams) in isopropyl alcohol (150 ml) was heated to reflux temperature. The reaction mixture was cooled to 50-55°C and unwanted precipitate was removed by filtration. Distilled off the solvent completely from filtrate under reduced pressure to get the title compound (trans - isomer).

Yield: 7.4 grams.

Example-5: Preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one (formula-6).

To a mixture of magnesium(19.5 grams) and iodine(0.8 grams) in 1000 ml of methanol was added 40 grams of ll-chloro-2,3-dihydro-2-methyl-lH-dibenz[2,3:6,7] oxepino [4,5-c] pyrrol-l-one at 25-30°C and stirred the reaction mixture for 30 minutes at 25-30°C. Heated the reaction mixture to reflux temperature and stirred for 1 hr at reflux.. After completion of the reaction, the reaction mixture was cooled to 25-30°C and water (400 ml) was added. Adjusted the pH of the reaction mixture to 6.4 by using 20 % Dil. HC1 at 10-15 °C. Ethyl acetate (600 ml) was added to the reaction mixture and stirred for 30 minutes. Both the organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed with 10% NaC1 solution. Distilled off the solvent completely under reduced pressure. Isopropyl alcohol (120 ml) was added to the obtained residue. The reaction mixture was cooled to 0-5°C and stirred for 2 hrs. Filtered the obtained solid, washed with isopropyl alcohol and dried to get the title compound. Yield: 21 grams.

Example-6: Preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one (formula-1).

To a solution of cis-ll-chloro-2,3,3a,12b-tetrahydro-2-methyl-lH-dibenz

[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-5 (15 grams) in toluene (225 ml) was added DBU (3.8 grams) at 15-20°C. The reaction mixture was raised to 25-30°C and stirred for 10-12 hours. Distilled off the solvent completely under reduced pressure to get the residue which contains mixture of cis and trans-isomers. Isopropyl alcohol (45 ml) was added to the obtained residue and heated to reflux temperature. The reaction mixture was cooled to 50-55°C and unwanted precipitate was removed by filtration. Distilled off the solvent completely from filtrate under reduced pressure to get the title compound (trans - isomer).

Yield: 7.5 grams: Melting Point: 140-143°C.

We claim:

1. An improved process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2- methyl-1 H-dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one compound of formula-1, comprises of,

Formula-1

a) Suspending a mixture of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2,

and l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), in a suitable inert solvent, and heating the reaction mixture at a suitable temperature for a suitable period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to high temperature to get a clear solution,

d) lowering the temperature of the solution to precipitate a solid,

e) filtering off the solid obtained and collecting the filtrate,

f) distilling off the solvent from the filtrate obtained in step-e), to provide trans-5- chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7] oxepino[4,5-c]pyrrol- 1-one compound of formula-1.

2. A process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-1, comprises of,

a) Suspending a mixture of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-1-one compound of formula-2 and 1,8-
Diazabicyclo[5.4.0]undec-7-ene (DBU), in a suitable inert solvent, and heating the reaction mixture at a suitable temperature for a suitable period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to higher temperature,

d) filtering the suspension and collecting the filtrate,

e) distilling off the solvent from the filtrate obtained in step-d), to provide trans-5- chloro-2,3,3a,12b-tetrahydro-2-methyHH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l- one compound of formula-1.

3. A process according to claim-1 and 2, wherein the suitable inert solvent used in step- a) is selected from "hydrocarbon solvents" like toluene, hexane, heptane and cyclohexane; and "chloro solvents" like dichloromethane, dichloroethane, carbon tetrachloride and chloroform or their mixture thereof.

4. A process according to claim-1 and 2, wherein the suitable inert solvent used in step-a) is toluene.

5. A process for the preparation of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-l1H- dibenz[2,3,6,7]oxepino[4,5-c] pyrrol-l-one compound of formula-1, comprises of,

a) Suspending a mixture of cis and trans isomers of 5-chloro-2,3,3a,12b-tetrahydro- 2-methyl-1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one in a isopropyl alcohol,

b) heating the suspension to higher temperature,

c) filtering the suspension and collecting the filtrate,

d) distilling off the solvent from the filtrate obtained in step-c), to provide trans-5- chloro-2,3,3a, 12b-tetrahydro-2-methyl- 1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l - one compound of formula-1.

6. A process for the preparation of cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7] oxepino[4,5-c]pyrrol-l-one compound of formula-2, comprises of,

a) Reacting 5-chloro-2,3-dihydro-2-methyl-1 H-dibenz[2,3:6,7]oxepino[4,5-c] pyrrol-l-one compound of formula-3,

Formula-3 with magnesium in presence of catalytic amount of iodine in methanol,

b) heating the reaction mixture to reflux temperature and cool the reaction mixture and quench the reaction mixture with water,

c) adding ethyl acetate to the reaction mixture and stirred,

d) concentrating the organic layer obtained in step-c) and adding appropriate amount of isopropyl alcohol and concentrate to obtain cis-5-chloro-2,3,3a,12b-tetrahydro- 2-methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2 as a solid,
e) filtering the mixture to isolate the solid and optionally recrystallizing it using isopropyl alcohol to provide pure cis-5-chloro-2,3,3a,12b-tetrahydro-2-methyl- 1H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-2.

7. An improved process for the preparation of trans-ll-chloro-2,3,3a,12b-tetrahydro-2-
methyl-lH-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-6, comprises of,

a) Suspending a mixture of cis-1 l-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-5 and 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU), in a suitable inert solvent, and heating the reaction mixture at a suitable temperature for a suitable period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to high temperature to get a clear solution,

d) lowering the temperature of the solution, preferably to about 50°-60°C, more preferably to 50°- 55°C to precipitate a solid,

e) filtering off the solid obtained and collecting the filtrate,

f) distilling off the solvent from the filtrate obtained in step-e), to provide trans-11- chloro-2,3,3a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-1 - one compound of formula-6.

8. A process for the preparation of trans-11 -chloro-2,3,3a, 12b-tetrahydro-2-methyl-1H- dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-6, comprises of,

a) Suspending a mixture of cis-1 l-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz [2,3,6,7]oxepino[4,5-c]pyrrol-l-one compound of formula-5 and 1,8-Diaza bicycle [5.4.0]undec-7-ene (DBU), in a suitable inert solvent, and heating the reaction mixture at a suitable temperature for a suitable period of time,

b) distilling off the solvent to provide a residue,

c) adding isopropyl alcohol to the residue obtained in step-b) and heating the suspension to higher temperature,

d) filtering the suspension and collecting the filtrate,

e) distilling off the solvent from the filtrate obtained in step-d), to provide trans-5- chloro-2,3,3 a, 12b-tetrahydro-2-methyl-1 H-dibenz[2,3,6,7]oxepino[4,5-c]pyrrol-1 - one compound of formula-6.

9. A process according to claim-7 and 8, wherein the suitable inert solvent used in step- a) is selected from "hydrocarbon solvents" like toluene, hexane, heptane and cyclohexane; and "chloro solvents" like dichloromethane, dichloroethane, carbon tetrachloride and chloroform or their mixture thereof.

10. A process according to the proceeding claims, the suitable temperature is 0°C to reflux temperature of the solvent used in the reaction and the suitable time period is up to the conversion of 'cis' isomer into 'trans' isomer.