FIELD OF INVENTION

The invention relates to a novel process for the preparation of (S,S)-2, 8-Diazabicyclo(4, 3, 0) Nonane of Formula I

Which is useful as an intermediate in the preparation of Moxifloxacin.

BACKGROUND OF INVENTION

The present invention is directed to an improved industrially viable, cost effective process for manufacturing (S,S)-2,8-Diazabicyclo[4.3.0]nonane in a substantially pure form and consequent conversion to Moxifloxacin
and its pharmaceutically acceptable salts thereof.

(S,S)-2,8-diazabicyclo [4.3.0]nonane of Formula I is an important intermediate in the manufacture of many pharmaceutically active ingredients. Several processes are known in the literature for the preparation of this intermediate.

EP 350733 and CA 1340553 discloses a process for the preparation of 2,8-diazabicyclo[4.3.0] nonane which comprises of catalytical hydrogenation of 8-benzyl-5H-pyrrolo[3,4-b]pyridine-5,7(6H)- dione of Formula II using H 2 /Ru-C or Pd/C to give 8-benzyl-2,8-Diazabicyclo[4.3.0]nonane-7,9-dione of Formula III followed by reduction in presence of LiAlH4 or NaBH4 VBFS-(C2Hs)20 to give 8-benzyl- 2,8-diazabicyclo[4.3.0]nonane of Formula IV. The compound of Formula IV is further debenzylated using H 2 /Pd to form a racemic mixture of 2,8-diazabicyclo[4.3.0]nonane of Formula I which is depicted in the following scheme.

The main disadvantage of this process involves handling and use of LiAlFLi for reduction, which is hazardous and economically less viable at commercial scale.

US 5770597, EP 690862 discloses a process for preparing (S,S)-2,8 diazabicyclo[4.3.0]nonane from pyridine dicarboxylate. The process comprises esterification of the di acid of Formula V in presence of thionyl chloride and methanol to form an ester of Formula VI which is reduced in the presence of L1AIH4 to form to a diol of Formula VII .This diol is further chlorinated, brominated or methane sulphonated to form a compound of Formula VIII and cyclised in the presence of tosylamide and sodium hydride to give a compound of Formula IX .The compound of formula IX is hydrolyzed in the presence of 48% hydrobromic acid to give compound of formula X, converted to suitable salt form of formula XI and hydrogenated to give compound of Formula I which is shown in the following scheme.

The disadvantage of this patent involves protection, de protection twice, which increases the number of steps and affects the overall yield of the product. Also it involves handling and use of LiAlH4 for reduction, which is hazardous and economically less viable at commercial scale.

The present invention discloses an efficient method for the preparation of (S,S)-2, 8-Diazabicyclo(4, 3, 0) Nonane of Formula I.

OBJECTIVE OF THE INVENTION

An object of the present invention is to provide a process for the preparation of (S,S)-2,8-diazobicyclo[4.3.0] nonane of Formula I
using catalytic hydrogenation with milder conditions.

SUMMARY OF THE INVENTION

The instant invention discloses an Novel and efficient method for the preparation of (S,S)-2,8-diazobicyclo[4.3.0] nonane the Formula I
Which comprises reducing the compound of Formula II by catalytic hydrogenation in presence of ammonium formate.

DETAILED DESCRIPTION OF THE INVENTION

The present invention describes a novel process for the preparation of (S,S)-2,8-diazobicyclo[4.3.0] nonane compound of formula I from compound of formula II.

We have surprisingly found that the compound of Formula I can be prepared in good yield and high purity by catalytic hydrogenation of compound of formula II with various hydrogenating agents in presence of ammonium formate under milder reaction conditions.

The various hydrogenating agents may include palladium on charcoal, Raney-Nickel etc. Most preferably in Palladium on charcoal.

The catalytic hydrogenation of compound of formula II is effected in a suitable reaction media which includes alcohols like methanol, ethanol, isopropyl alcohol etc and more preferably methanol.

Optionally, the above catalytic hydrogenation is conducted in presence of additional hydrogen source like ammonium formate.

Normally, conventional hydrogenation procedure, although often offers selective reduction, it requires a special set of apparatus and is always associated with the usual risk of using hydrogen gas. However, in the present process of the invention this reaction is carried out with a hydrogenation source in presence of a metal catalyst such as palladium, Raney nickel etc.
The hydrogenation is conveniently effected at elevated temperatures. Most conveniently at reflux temperature of the reaction mixture. The reaction may be conveniently carried out by applying pressure or without applying pressure to the reaction vessel.

After completion of the reaction as monitored by TLC, the catalyst is removed by filtration and subsequently washed with methanol. The obtained filtrate, on evaporation under reduced pressure gives the crude compound which was further purified by distillation to give compound of formula I.

The compound obtained by the above process is characterized by spectroscopic methods.

The compound of formula I is further converted to Moxifloxacin.

The following examples further illustrate the specific aspects of the present process and are not intended to limit the scope thereof in any respect and should not be so construed.

EXAMPLE

A solution of (S,S)-8-benzyl-2,8-diazabicyclo[4,3,0] nonane (65gm, 0.303 mol) and equal weight of 5% Pd/C in methanol (540ml), are refluxed in the presence of anhydrous ammonium formate (92.63gm, 1.518mol) was added in a single portion under Nitrogen atmosphere. After completion of reaction as monitored by Thin Layer Chromatography (TLC) the catalyst is removed by filtration and subsequently washed with methanol. The obtained filtrate, on evaporation under reduced pressure at below 60°C to give the crude compound 38gm of (S,S)- 2,8-diazabicyclo[4,3,0] nonane. which was further purified to give compound of formula I.

Weight: 35 gm

CLAIMS:

1) A process for the preparation of compound of formula I

which comprises reducing the compound of Formula II

by catalytic hydrogenation in presence of ammonium formate.

2) The process according to claim 1, where the catalytic hydrogenation of compound of formula II is carried out an organic solvent.

3) The process according to claim 2, where an organic solvent is an alcohol.

4) The process according to claim 3, an organic solvent is alcohol like methanol, ethanol and more preferably in methanol.