FIELD OF INVENTION

[001] This invention relates to a process for the preparation of N-amino-substituted 3.3.0 azabicyclo octane, an intermediate for the preparation of gliclazide, an anti-diabetic drug.

BACKGROUND OF INVENTION

[002] The present invention relates to a process for the preparation of N-amino derivative of 3.3.0 azabicyclo octane, which is used in the preparation of gliclazide, an anti-diabetic drug. Prior art search revealed a few methods of synthesizing the said compound by employing different reactants.

[003] Patent No. JP 05 – 065270 discloses a method of preparing the said compound by reacting 3-azabicyclo[3,3,0]octane with a nitrite in an acidic solution and then continuously reducing it without a treatment by using a powdery metal.

[004] US Patent No. 6,222,071 discloses a process of N-amino-3-azabicyclo[3.3.0]octane preparation, by reacting NH2Cl and 3-azabicyclo[3.3.0]octane, wherein 3-azabicyclo[3.3.0]octane has been prepared according to the process described in patent Specification EP 277 267.

[005] Formation of 3,4-diazabicyclo[4.3.0]non-2-ene and N,N-aza-3-bicyclo[3.3.0]octane by alicyclic hydrazine rearrangement has been reported in Monastaste fuer chemie (1994), 125 (10), 1113-20 by Delalu, H et al.

[006] But the aforementioned processes employ either N-nitrosation of 3-azabicyclo[3.3.0]octane followed by reduction of the- nitroso group or direct amination of 3-azabicyclo[3.3.0]octane by chloramine. Given the carcinogenicity of nitrosamines it is difficult to employ the process as disclosed in (Patent No. JP 05 – 065270). Coming to direct amination using chloramine that has been generated in the solution by an exothermic reaction, it is highly risky in handling such explosive reactions even under extreme controlled conditions.

[007] In order to overcome the above difficulties the present invention comes out with a suitable method of preparing N-amino-3-azabicyclo[3.3.0]octane, an intermediate in the preparation of an anti-diabetic drug, Gliclazide.

OBJECT OF INVENTION

[008] The primary object of the invention is to provide a process for the preparation of N-amino-3-azabicyclo[3.3.0]octane.

[009] Another object of the invention is to provide a process for the preparation of N-amino-3-azabicyclo[3.3.0]octane which is an important intermediate for the preparation of anti-diabetic drug, Gliclazide.

STATEMENT OF INVENTION

[0010] The invention provides a process for the preparation of N-amino-3-azabicyclo[3.3.0]octane. The process involves the reaction of dimesylate of cis-1,2-cyclopentanedimethanol with hydrazine hydrate at about 60-80oC in the presence of a C1-C4 alcohol such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-2-propanol, 2-methyl-1-propanol.

DETAILED DESCRIPTION OF INVENTION

[0011] The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.

[0012] The present invention pertains to a process for the preparation of N-amino-3-azabicyclo[3.3.0]octane of Formula (I)

Formula (I)

[0013] In embodiment of the invention, the process of preparation of N-amino-3-azabicyclo[3.3.0]octane is a single step process. The process involves the reaction of dimesylate of cis-1,2-cyclopentanedimethanol with hydrazine hydrate at a temperature in the range of 60-80oC, in the presence of a methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-2-propanol, 2-methyl-1-propanol or any C1-C4 alcohol. The said reaction directly produces N-amino-3-azabicyclo[3.3.0]octane which can be readily be isolated from the reaction mixture using techniques well known in the art.

[0014] The invention is further illustrated by the following example(s), which should not be construed to limit the scope of the invention in anyway.

Example:

Scheme:

Procedure:

[0015] A 500ml 3-necked round bottomed flask fitted with a water cooled condenser, an overhead stirrer, a thermometer pocket and a 100ml dropping funnel is charged with mesylate product (M.P: 56-57oC, 20g, 0.069Mol, 1 equiv.) and methanol (d =0.791; B.P: 64.7oC) 0.1 L.

[0016] The mixture is continuously stirred at room temperature (25-27oC). To the mixture, hydrazine hydrate (0.02kg, 0.0419mol, 6 equiv.) is added drop wise through a dropping funnel while maintaining the temperature of the reaction mixture below 30oC. After completion of addition, the mixture is heated to a temperature in the range of 60-80oC. Reaction mixture is then refluxed for 5 hours. After 5 hours, product formation is confirmed by Thin Layer Chromatography (TLC) [mobile phase (70 hexane: 30 ethyl acetate)]. Once the reaction is completed, the entire methanol is concentrated on a rotary evaporator through vacuum at a temperature of 45-50oC. 0.1 L of water is added and then extracted with dichloro methane (0.1 L x 3 times). The extract is then dried over Na2SO4 and all the dichloro methane is concentrated. The product is a light yellow oily liquid.

[0017] The yield obtained as per the procedure was found to be 8.5gm with 96% purity.

[0018] The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

STATEMENT OF CLAIMS

We claim,

1. A process for the preparation of N-amino-3-aza-bicyclo[3.3.0]octane, the process comprising:

reacting dimesylate of cis-1,2-cyclopentanedimethanol with hydrazine hydrate in the presence of a C1-C4 alcohol.

2. The process for the preparation of N-amino-3-aza-bicyclo[3.3.0]octane as claimed in claim 1, wherein the reaction takes place in the range of 60-80oC.

3. The process for the preparation of N-amino-3-aza-bicyclo[3.3.0]octane as claimed in claim 1, wherein the C1-C4 alcohol is selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-2-propanol, 2-methyl-1-propanol.