Field of the Invention
The present invention relates to an improved process for reducing esters. Particularly, the present invention relates to an improved process of reducing esters of organic compounds into corresponding alcohols. More particularly the present invention relates to preparation of alcohols compound of formula (I)

by reducing ester compound of formula (II).

Background of the Invention
Ester compounds and the corresponding reduced alcohols are important intermediates for the preparation of many pharmaceutical agents. For example 2-pheny 1-1,3-propane diol is an important intermediate used in the preparation of Felbamate an antiepileptic drug used in the treatment of epilepsy. Felbamate is used alone or together with other medicines to control partial seizures (convulsions) in the treatment of epilepsy. Its chemical name is 2-pheny 1-1,3-propanediol dicarbamate. Similarly, quinuclidine-3-methanol is an important intermediate used in the preparation of Mequitazine an antihistamine and anticholinergic, which is used to treat allergies and rhinitis.
US 2,884,444 discloses a process for preparing 2-phenyl-l,3-propane diol by reducing diethyl phenylmalonate using LAH in ether solvent, which is notoriously volatile, flammable and explosive.
US 4,982,016 discloses a process for the preparation of 2-phenyl-l,3-propanediol by dissolving lithium aluminum hydride and lithium borohydride in tetrahydrofuran, cooling the solution and slowly adding diethyl phenylmalonate and dry xylene, heating and maintaining the solution at 135 °C. Lithium aluminium hydride reacts violently with water and liberates hydrogen, which is likely to cause the

material ignite. Thus, for large scale production, use of lithium aluminium hydride is undesirable from safety and environmental point of view. Further this patent requires high temperature which makes the process not suitable in terms of industrial point of view.
US 5,091,595 discloses the use of diisobutylaluminum hydride (DIBAL) in THF at low temperatures and US 4,335,012 discloses the use of vitride in benzene for the reduction of diethyl phenylmalonate. Being carcinogenic solvent, benzene is not suitable for industrial point of view and the use of DIBAL requires maintenance of low temperature.
WO 2012/0325082 provides a process in which 2-phenyl-l,3-propanediol is obtained by reducing diethyl phenylmalonate with sodium borohydride (NaBH4) in the presence of an alkali metal dihydrogen phosphate buffer or the hydrate thereof.
EP 0 820 439 discloses a process for the preparation of 2-benzyl-l,3-propandiol from the corresponding diester using a sodium borohydride or lithium aluminum hydride.
In addition several literatures provides a process for reducing diethyl phenylmalonate for examples, Zhongguo Xinyao Zazhi, 2005, 14(12), Page: 1443-1444 utilizes sodium borohydride in methanol/water; Huaxue Shiji, 2009, 31(12), 1039-1040 discloses the use of sodium borohydride in the presence of sodium methoxide and Research Reports of Toyama National College of Technology, 2001, Vol 35 disclose the use of nonflammable reducing agent sodium borohydride in the presence of Hydrochloric acid.
Despite several prior art, as discussed above, provides a process for the reduction of ester into alcohol, i.e. process for the preparation of 2-phenyl-l,3-propanediol from diethyl phenylmalonate the said art has several drawbacks : 1) The process is low yielding 2) Requirement of anhydrous conditions 3) use of hazardous reducing agents 4) use of flammable solvent like ether and carcinogenic solvent like benzene and 5) high impurity levels when HC1 is used as solvent.
In view of this there is a need to provide simple, high yielding, cost effective, eco-friendly, environmentally safe, and, industrially feasible, process for reducing esters that does not require stringent process conditions, sophisticated infrastructure

and especially skilled personnel. With our continued research for developing a process for the preparation of alcohol of formula (I) or its salts, we have identified a process, in which the compound of general formula (I) obtained in high yield.
Objectives of the invention
The main objective of the present invention is to provide a simple and commercially viable, industrially scalable process for the preparation of compound of the formula (I).
Another objective of this invention is to provide a method for the preparation of compound of the formula (I) that avoids hazardous reagents and solvents, thereby making the process environmentally safe, sound and beneficial.
One more objective of the present invention is to provide a robust, high yield process for reducing ester into alcohol at ambient temperature.
Summary of the invention
Accordingly, the primary aspect of the present invention provides an improved process for the preparation of alcohol of compound of formula (I),

said process comprises reducing ester of compound of formula (II)

wherein Cy represents cyclic ring, R1 represent Ci to C6 alkyl or aryl; m is 0 or 1; n is 0 or 1; o is 0 or 1; R represents hydrogen, alkyl, or -C(=)-OR1 with a proviso that when m and n is 0, R is 0, with a reducing agent in the presence of alcoholic ammonia solution.
Detailed Description
The main embodiment of the present invention relates to an improved process for the preparation of alcohol compound of formula (I),


said process comprises the step of reducing the ester compound of formula (II)

wherein Cy represents cyclic ring selected from cycloalkyl, aryl, heteroaryl, heterocyclyl and R1 represent C\ to C6 alkyl group or aryl; m is 0 or 1; n is 0 or 1; o is 0 or 1; R represents hydrogen, alkyl, or -C(=)-OR1 with a with a proviso that when m and n is 0, R is 0, with a reducing agent in the presence of alcoholic ammonia solution.
In another embodiment of the present invention, the reducing agent used is selected from sodium borohydride in water.
The term Q to C6 alkyl group represents linear or branched such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, t-butyl, n-pentyl, isopentyl, hexyl and the like; Aryl group represents phenyl, napthyl and the like; cycloalkyl represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; heteroaryl represents pyridyl, pyrimidinyl, piperazinyl, thienyl, furyl, indolyl and the like; heterocyclyl represents piperadinyl, piperazinyl, pyrrolidinyl, azabicyclo (2,2,2)octane and the like.
In another embodiment, alcoholic ammonia includes methanolic ammonia, ethanolic ammonia and the like.
Applicant found that the use of acidic medium like HC1 as reaction medium yields the product with low purity and contacting the reaction with neutral condition in the presence of buffer suffers in terms of poor yield. Surprisingly applicant found the use of alcoholic ammonia like methanolic ammonia proceeds smoothly at room temperature, thereby avoids the utility cost, and yield the final product with higher yield and purity.
In still another embodiment of the present invention, the reduction proceed smoothly at room temperature thereby avoids the stringent requirement of maintaining at low temperature or high temperature as required by prior art processes.

In yet another embodiment of the present invention, isolation of compound of formula (I) can be done by conventional technique such as filtration, centrifugation, decantation, extraction, distillation, and the like.
In another embodiment, the preferred compounds of formula include : 2-Phenyl-1,3-propanediol and quinuclidine-3-methanol.
In another embodiment, the compounds of formula (I) prepared according to the present invention are converted to pharmaceutically active compounds such as Felbamate, Mequitazine.
In a preferred embodiment, the present invention provide an improved process for the preparation of Felbamate of compound of formula (III),

which comprises the steps of
(i) reducing compound of formula (Ha)

wherein R1 represent Ci to C6 alkyl group or aryl; with a reducing agent in the presence of alcoholic ammonia solution to give 2-phenylpropane-l,3-diol of formula (la)
and
(ii) converting the diol of formula (la) to Felbamate or its pharmaceutically acceptable
salts.
In another embodiment, dialkyl phenyl malonate of formula (Ha) represents diethyl phenyl malonate, dimethyl phenyl malonate and the like.

In another preferred embodiment, the present invention provide an improved process for the preparation of Mequitazine of compound of formula (IV),

which comprises the steps of
(i) reducing compound of formula (lib)

wherein R1 represent Q to C6 alkyl group or aryl, with a reducing agent in the presence of alcoholic ammonia solution to give quinuclidine-3-methanol of formula (lb)
and
(ii) converting the diol of formula (lb) to Mequitazine or its pharmaceutically
acceptable salts.
The following examples are provided by way of illustration only and should not be construed to limit the scope of the invention.
Example 1:
Preparation of 2-Pheny-l,3-propanediol:
To methanolic ammonia (250 mL; 12%), diethyl phenyl malonate (50 g), sodium
o
borohydride (16.7 g ) in water (50 mL) were added at 15-20 C and the mass was stirred at 25-30 °C till completion of reaction. After completion of reaction, methanol was distilled out and the reaction mixture was quenched by adding water. The reaction mass optionally heated and the solution was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulphate and evaporated to yield 2-phenyl-1,3-propane diol (>25 g).

EXAMPLE-2
Preparation of quinucIidine-3-methanoI
To the solution of (50g) of methyl- 1-azabicyclo (2,2,2)octane-3-carboxylate in 250ml of methanolic ammonia (12%) cooled to 15-20 °C, the solution of the 16.7g of sodium borohydride in 50ml of water was added in 30-40 min. The mixture was stirred for 3 hours at 25-30 °C and the methanol was distilled out The reaction mixture was quenched by adding 90ml of water followed by heating to 50-60 °C for 1 hour, the solution was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulphate and evaporated to dryness to yield quinuclidine-3-methanol (30g) with purity 90-95%.
Given below is the comparison of yields obtained with the reducing agent of the
present invention with the prior art reducing agents.
Table-1
This table list out the advantages or usage of KI under different molar equivalent.

* Starting from 50 g diethyl phenyl malonate
The above table clearly indicate the present invention provides high yield and avoids
hazardous reagents.
Advantages of the present invention:
> Avoids hazardous reducing agents and flammable solvent
> Produces the desired product in high yield.
> Reaction proceed smoothly at ambient temperature

We claim,
1. An improved process for the preparation of alcohol of compound of formula
(I),
said process comprises reducing ester of compound of formula (II)

wherein Cy represents cyclic ring, R represent Q to C(, alkyl or aryl; m is 0 or 1; n is 0 or 1; o is 0 or 1; R represents hydrogen, alkyl, or -C(=)-OR1 with a with a proviso that when m and n is 0, R is 0, with a reducing agent in the presence of alcoholic ammonia solution.
2. The process as claimed in claim 1, wherein the reducing agent is selected from sodium borohydride in water
3. The process as claimed in claim 1, alcoholic ammonia is selected from methanolic ammonia or ethanolic ammonia.
4. The process as claimed in claim 1, wherein Aryl group represents phenyl, napthly and the like; cycloalkyl represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl; heteroaryl represents pyridyl, pyrimidinyl, piperazinyl, thienyl, furyl, indolyl; heterocyclyl represents piperadinyl, piperazinyl, pyrrolidinyl, azabicyclo (2,2,2)octane.
5. The process as claimed in claim 1, wherein the reaction is carried out at room temperature.
6. The process as claimed in claim 1, wherein the the preferred compounds of formula (I) are selected from 2-Pheny-1,3-propanediol; quinuclidine-3-methanol and 2-benzyl-1,3-propanediol.

7. The process as claimed in claim 1, wherein the compounds of formula (I) prepared according to the present invention are converted to pharmaceutically active compounds.
8. The process as claimed in claim 7, wherein the pharmaceutically active compound are selected from Felbamate, Mequitazine.
9. An improved process for the preparation of 2-phenylpropane-l,3-diol of formula (la)

which comprises the steps of
(i) reducing compound of formula (Ha)
wherein R1 represent Q to C6 alkyl group or aryl; with a reducing agent in the presence of alcoholic ammonia solution.
10. The process as claimed in claim 9 for the preparation of Felbamate of
compound of formula (III),
which comprises converting the diol of formula (la) to Felbamate or its pharmaceutically acceptable salts.

11. An improved process for the preparation of quinuclidine-3 -methanol of
formula (lb)
which comprises the steps of
(i) reducing compound of formula (lib)

wherein R1 represent Q to C6 alkyl group or aryl, with a reducing agent in the presence of alcoholic ammonia solution.
12. The process as claimed in claim 11 for the preparation of Mequitazine of
compound of formula (IV),

which comprises converting the diol of formula (lb) to Mequitazine or its pharmaceutically acceptable salts.