Field of the Invention:
The present invention relates to a novel process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound represented by the following structural formula-1.

Background of the Invention:
N-butyl-2-((4R,6S)-6-fonnyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-1 was disclosed in PCT publication number WO 2008/044243 as an important intermediate in the preparation of statin compounds (HMG-CoA reductase inhibitors). The said publication also disclosed different process for the preparation of compound of formula-1. The disclosed process involves number of steps and column chromatographic purification at each stage which makes the process commercially not suitable.
Statin compounds like rosuvastatin, pitavastatin, fluvastatin, atorvastatin, simvastatin, lovastatin, are important drugs used for treatment of cholesterol reduction. Hence it is advantageous to have novel and efficient process for the preparation of important intermediate like N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-1, so that they can be used effectively in the preparation of statin compounds.
Hence the main aspect of the present invention is to provide novel and efficient process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compound of formula-1, an important intermediate in the preparaiton of statin compoimds, which is more effective and easy to scale up to commercial level in a convenient and cost effective manner.
Brief description of the Invention:
The first aspect of the present invention is to provide a process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-1, which comprises of the following steps;

a) reacting the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of formula-2 with n-butyl amine in methanol and in presence or absence of a base, to provide the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5,
b) oxidizing the compound of formula-5 with a suitable oxidizing agent in presence of a catalyst in a suitable solvent to provide the compound of formula-1.
Further the invention also includes the above reaction carried without the isolation of compound formula-5 and oxidizing it in-situ with a suitable oxidizing agent and a solvent to provide the compound of formula-1.
The second aspect of the present invention is to provide a novel process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l ,3-dioxan-4-yl)acetamide compound of formula-1, which comprises of the following steps:
a) Hydrolyzing the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-2 with a suitable base in a suitable solvent provides the 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetic acid compound of formula-3,
b) treating the compound of formula-3 with dimethylsulfate in presence of a suitable base in methanol to provide the methyl 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-4,
c) reacting the compound of fonnula-4 with n-butyl amine in presence or absence of a base and solvent, provides the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5,
d) oxidizing the compound of fonnula-5 with a suitable oxidizing agent in presence of a catalyst in a suitable solvent to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-1.
The third aspect of the present invention is to provide another process for the preparation of compound of formula-1, which comprises of the following steps a) reacting the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of formula-6 with a suitable base in methanol to provide

the methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l ,3-dioxan-4-yl)acetate compound of fonnula-4,
b) reacting the compound of fonnula-4 with n-butyl amine in presence or absence of a solvent to provide the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5,
c) oxidizing the compound of formula-5 with a suitable oxidizing agent in presence of a catalyst in a suitable solvent to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compoxmd of formula-1.
Further aspect of the present invention is to provide a process for the preparation of ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-6, which comprises of the following steps;
a) Reacting the (S)-4-chloro-3-(trimethylsilyloxy)butanenitrile compound of formula-7 with ethyl bromo acetate compound of formula-8 in presence of zinc dust and a suitable acid in a suitable solvent to provide the (S)-ethyl 6-chloro-5-hydroxy-3-oxohexanoate compound of formula-9,
b) reducing the compoimd of formula-9 by treating it with diethyl methoxy borane in presence of a suitable reducing agent in a suitable solvent to provide the (3R,5S)-ethyl 6-chloro-3,5-dihydroxyhexanoate compound of formula-10,
c) treating the (3R,5S)-ethyl 6-chloro-3,5-dihydroxyhexanoate compound of formula-10 with 2,2-dimethoxy propane in presence of an acid in a suitable solvent to provide the ethyl 2-((4R,6S)-6-(chloromethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-11,
d) reacting the compound of formula-11 with sodium acetate in presence of a phase transfer catalyst in a suitable solvent to provide the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate, compound of formula-6.
Advantageous of the Present invention:
• Avoids column chromatograhy purifications
• One pot process for compoud of formula-1 which provides high yeild and purity
• Reduction in niunber of steps lead to the decrese in time cycle.
• Eco-friendly and commercially viable process

Detailed description of tlie Invention:
As used herein present invention the term "suitable base" refers to the bases selected from "alkali metal hydroxides" such as sodium hydroxide, potassium hydroxide and the like; "alkali metal carbonates" such as sodium carbonate, potassium carbonate, cesium carbonate and the like; "alkali metal bicarbonates" such as sodium bicarbonate, potassium bicarbonate and the like; "alkali metal alkoxide" such as sodium methoxide, sodium tertiary butoxide and potassium tertiary butoxide and the like;
As used herein the presented invention, the term "suitable solvent" refers to the solvents selected from "polar solvents" such as water; "polar aprotic solvents" such as dimethylsulfoxide, dimethylacetamide, dimethyl formamide and tetrahydrofliran; nitrile solvents such ass acetonitrile and the like; "alcohol solvents" such as methanol, ethanol, n-propanol, isopropanol and n-butanol and the like; "chloro solvents" such as methylene chloride, ethylene dichloride, carbon tetra chloride, chloroform and the like; "ketone solvents" such as acetone, methyl ethyl ketone, diethyl ketone, methyl tert-butyl ketone, isopropyl ketone and the like; "esters solvents" such as ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like; and their mixtures thereof
The term "statins" used herein the the present invention refers to the HMG-CoA reductase inhibitors like rosuvastatin, pitavastatin, fluvastatin, atorvastatin, simvastatin, lovastatin and other dihydroxy acid HMG-CoA reductase inhibitors.
Accordingly the present invention provides a novel process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-1.
The first aspect of the present invention provides a process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-1,


which comprises of the following steps;
a) Reacting the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)
acetate of formula-2,

with n-butyl amine in methanol and in the presence or absence of a base provides the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5,

b) oxidizing the compound of formula-5 with suitable oxidizing agent selected from
sodium hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-l-
piperidinyloxy, free radical)/KBr or oxalyl chloride/dimethyl sulfoxide in a suitable
solvent to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)
acetamide compound of formula-1.
Further the invention also provides a one pot process for the preparaiton of compound of formula-1, wherein the compound of formula-5 is not isolated and futher oxidized in-situ with a suitable oxidiziing agent and solvent as described above to provide the compound of formula-1.
As per the prior art, the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compound of formula-1 prepared by the reaction of (3R,5S)-tert-butyl 3,5,6-trihydroxy hexanoate with n-butylamine at 70-80°C to provide the (3R,5S)-N-butyl-3,5,6-trihydroxyhexanamide, which on further reaction with 2,2-dimethoxy

propane to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide followed by oxidation with oxalyl chloride provides the compound of formula-1. The said process involves colunm chromatography purification in each stage and the amidation reaction take place without usage of solvent. When the present inventor working on the same reaction, tt was surprisingly found that the n-butyl amine reaction with protected dihydroxy compound i.e., tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate in presence of methanol solvent provides the compound with high purity and yield. However at the same time, it was observed that when ethanol is used in place of methanol the said reaction was not proceed further.
In a preferred embodiment of the present invention, the process for the preparation of compound of formula-1 comprises of the following steps,
a) Reacting the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of formula-2 with n-butyl amine in methanol in presence of a suitable base like alkali metal carbonates, preferably potassium carbonate to provide the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compound of formula-5,
b) oxidizing the compoimd of formula-5 in-situ with a suitable oxidizing agent preferably with sodium hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy, free radical)/KBr in a suitable solvent preferably chloro solvents like methylene chloride to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compound of formula-1.
Further the reaction between compond of formula-2 with n-butyl amine of step a) also be carried out with out using any base under nitrogen pressure.
The second aspect of the present invention provides a novel process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-1, which comprise of the following steps;
a) Hydrolyzing the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of formula-2


with a suitable base in a suitable solvent, to provide the 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetic acid compound of formula-3,

b) treating the compound of formula-3 with dimethylsulfate in presence of a suitable
base in a suitable solvent, to provide the methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-
dimethyl-1,3-dioxan-4-yl)acetate compound of formula-4,

c) reacting the compound of formula-4 with n-butyl amine in presence or absence of a
solvent and base to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-
dioxan-4-yl)acetamide compound of formula-5,

d) oxidizing the compound of formula-5 with a suitable oxidizing agent like sodium
hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-l-
piperidinyloxy, free radical)/KBr or oxalyl chloride/dimethyl sulfoxide in a suitable
solvent to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)
acetamide compound of formula-1.
In a preferred embodiment of the present invention, the process for the preparation of compound of formula-1 comprises of the following steps, a) Hydrolyzing the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate of formula-2 with a suitable base like alkali metal hydroxides, preferably

sodium hydroxide in a suitable solvent like polar aprotic solvent, preferably tetrahydrofuran provides the 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetic acid compound of formula-3,
b) treating the compound of formula-3 with dimethylsulfate in presence of a suitable base like alkali metal bicarbonate, preferably sodium bicarbonate in a suitable solvent like alcoholic solvent, preferably methanol to provide the methyl 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of fonnula-4,
c) reacting the compound of formula-4 with n-butyl amine to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l ,3-dioxan-4-yl)acetamide compound of formula-5,
d) oxidizing the compound of formula-5 with a suitable oxidizing agent preferably sodium hypochlorite in presence of a catalyst like TEMPO/KBr in a suitable solvent like chloro solvent, preferably methylene chloride provides the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-1
The third aspect of the present invention provides another process for the preparation of compoxind of formula-1, which comprise of the following steps
a) reacting the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)
acetate compoimd of formula-6

with a suitable base in methanol to provide the methyl 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-4,

b) reacting the compound of formula-4 with n-butyl amine in the presence or absence of
a solvent and base to provide the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-
dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5.


c) oxidizing the compound of formula-S with a suitable oxidizing agent in presence or absecne of a catalyst in a suitable solvent to provide the N-butyl-2-((4R,6S)-6-fomiyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-l.
In a preferred embodiment of the present invention, the process for the preparation of compound of formula-l comprises of the following steps,
a) reacting the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of formula-6 with a suitable base like alkali metal carbonate, preferably potassium carbonate in methanol to provide the methyl 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-4,
b) reacting the compound of formula-4 with n-butyl amine in the absence of a solvent and base to provide the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5,
c) oxidizing the compound of formula-5 with sodium hypochlorite in presence of a catalyst like TEMPO/KBr in methylene chloride to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-l.
Further the present invention provides a process for the preparation of ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-6,

which comprise of the following steps;
a) Reacting the (S)-4-chloro-3-(trimethylsilyloxy)butanenitrile compound of formula-7


with ethyl bromo acetate compound of formula-8

in presence of zinc dust and a suitable acid selected from methane sulfonic acid, para toluene sulfonic acid and the like, preferably methane sulfonic acid in a suitable polar aprotic solvent like tetrahydrofuran to provide the (S)-ethyl 6-chloro-5-hydroxy-3-oxohexanoate compound of fonnula-9,

b) reducing the compound of formula-9 by treating it with diethyl methoxy borane in
presence of a suitable reducing agent like sodium borohydride in a suitable solvent
selected from alcoholic solvents, polar aprotic solvents or mixtures thereof, preferably
mixture of solvent such as methanol and tetrahydrofuran, to provide the (3R,5S)-ethyl
6-chloro-3,5-dihydroxy hexanoate compound of formula-10,

c) treating the (3R,5S)-ethyl 6-chloro-3,5-dihydroxy hexanoate compoimd of
formula-10 with 2,2-dimethoxy propane in presence of a suitable acid selected from
methane sulfonic acid, para toluene sulfonic acid and the like, preferably methane
sulfonic acid in a suitable ketone solvent like acetone to provide the ethyl 2-
((4R,6S)-6-(chloromethyl)-2,2-dimethyI-1,3-dioxan-4-yl)acetate compound of
formula-11,

d) reacting the compound of formula-11 with sodium acetate in presence of a phase
transfer catalyst like tetrabutyl ammonium bromide, in presence or absence of a

solvent to provide the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of fonnula-6.
The N-butyl-2-((4R,6S)-6-fomiyl-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-] prepared as per the process described in the above aspects of the present invention can be converted into statin compounds by the methods known in the art.
The present invention further schematically represented by the following schemes: Scheme-1:

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-1: Preparation of (S)-ethyl 6-chloro-5-hydroxy-3-oxohexanoate:
Mixture of zinc dust (69 grams) and methane sulfonic acid (6 ml) in tetrahydofuran (500 ml) was heated to reflux temperature and stirred for an hour. (S)-4-chloro-3-(trimethylsilyloxy)butanenitrile (100 grams) followed by ethyl bromo acetate (147.2 grams) was added to the reaction mixture at 65-70°C and stirred. After completion of the reaction, reaction mixture was cooled to 25-30°C and then added to the aqueous hydrochloric acid solution at 0°C and stirred. The reaction mixture extracted into ethyl acetate and then washed it with sodium bicarbonate solution followed by sodiumchloride solution. Ethyl acetate was distilled off from the reaction mixture under reduced pressure to get the title compound. Yield: 116 grams
Example-2: Preparation of (3R,5S)-etliyI 6-chloro-3,5-dimethoxyhexanoate:
Diethyl methoxy borane (88ml) followed by sodium borohydride (16 grams) was added to a pre-cooled mixture of (S)-ethyl 6-chloro-5-hydroxy-3-oxohexanoate (110 grams) in tetrahydrofuran (550 ml) and methanol (220 ml) at -75°C under nitrogen atmosphere and stirred for 2 hrs. The reaction mixture was quenched with 50% hydrogen peroxide at 0°C. The reaction mixture was extracted into methylene chloride and washed it with 10% sodium bicarbonate followed by saturated sodium chloride solution. The methylene chloride layer was dried with sodium sulfate and distilled off under reduced pressure to get the title compound. Yield: 82 grams
ExampIe-3: Preparation of etiiyl 2-((4R,6S)-6-(chloro n)ethyI)-2-diniethyl-l-dioxan-4-yl)acetate:
2,2-dimethoxy propane (180 grams) followed by methane sulfonic acid (1,1ml) was added to a mixture of (3R,5S)-ethyl 6-cliloro-3,5-dihydroxy hexanoate (80 grams) and acetone (400 ml) at 25-30°C and stirred. After completion of the reaction, quenched

it with sodium bicarbonate solution and stirred. The reaction mixture was extracted in to petroleum ether and the washed it with saturated sodium chloride solution. The petroleum ether ftom the reaction mixture was distilled off under reduced pressure to get the title compound. Yield: 60 grams
ExampIe-4: Preparation of ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-13-dioxan-4-yl)acetate:
Mixture of ethyl 2-((4R,6S)-6-(chloromethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate (60 grams), tetra butyl ammonium bromide (79 grams) and anhydrous sodium acetate (61.2 grams) was heated to reflux temperature and stirred. After the completion of the reaction, the reaction mixture was cooled to 25-30''C and petroleum ether (50ml) was added to it then stirred for 60 minutes at 25-30°C. The reaction mixture was filtered and washed with petroleum ether. The solvent from the filtrate was distilled off under reduced pressure to get the title compound. Yield: 31 grams
Example-S: Preparation of methyl 2-((4R,6S)-6-(hydroxymethyI)-2,2-dimethyI-13-dioxan-4-yl)acetate:
Mixture of ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyM,3-dioxan-4-yl) acetate (80 grams), potassium carbonate (21 grams) in methanol (400 ml) was stirred for 2 hours at 0-10°C. The reaction mixture was quenched with water and then the reaction mixture extracted into methylene chloride and washed it with water. The methyl chloride from the reaction mixture was distilled off under reduced pressure to get the title compound. Yield: 64 grams
Example-6: Preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyI)-2,2-dimethyl-l-dioxan-4-yl)acetamide:
Mixture of n-butyl amine (100 grams), methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate (20 grams) was heated to reflux and stured. After completion of the reaction, distilled off n-butylamine under reduced pressure at below

60°C. The obtained residue was further purified using mixture of cyclohexane and ethyl
acetate.
Yield: 17 grams
Example-7: Preparation of N-butyl-2-((4R,6S)-6-formyl-2-dimethyH3-dioxan-4-yl)acetamide:
A solution of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetamide (6 grams) in methylene chloride (24 ml) was added to a pre-cooled mixture of TEMPO (0.01 gram), methylene chloride (36 ml) and potassium bromide (0.26 grams) at -5 to -15°C. Sodium hypo chloride (15.6 ml) was added to the reaction mixture at -15 to -5°C and stirred. After completion of the reaction, quenched it with 10% sodium thio sulfate solution at room temperature and water was added to it. Both organic and aqueous layers were separated and organic layer was washed with water followed by saturated sodium chloride solution. The solvent from organic layer was distilled off imder reduced pressure to get the title compound. Yield: 2.5 grams
Example-8: Preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-13-dioxan-4-yl)acetamide:
N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide (2 grams) in methylene chloride (10 ml) was added a mixture of oxalyl chloride (1.46 grams), dimethyl sulfoxide (1.36 ml) and methylene chloride (12 ml) at -65 to -60°C under nitrogen atmosphere and stirred for 45 minutes. Triethylamine (5 ml) was added to the reaction mixture at -65 to -60°C, stirred for 60 minutes and then added to ice-water. The reaction mixture was acidified with acetic acid solution and stirred. Both organic and aqueous layers were separated and organic layer washed with water followed by sodium chloride solution. The solvent from organic layer was distilled off under reduced pressure to get the title compound. Yield: 1.8 grams

Example-9: Preparation of 2-((4R,6S)-6-(hydroxyinethyi)-2,2-dimethyl-13-dioxan-4-yl)acetic acid:
Mixture of tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate (200 grams), sodium hydroxide (62 grams) in tetrahydrofuran (400 ml) was heated to reflux temperature and stirred up to completion of the reaction. The solvent from the reaction mixture was distilled off completely under reduced pressure at below 70°C to get the title compound. Yield: 300 grams
Example-10: Preparation of methyl 2-((4R,6S)-6-(hydroxymethyl)-2-dimethyl-13-dioxan-4-yl)acetate:
Dimethyl sulfate (195 grams) was added to a mixture of 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetic acid (200 grams), methanol (800 ml) and sodium bicarbonate (50 grams) at 0°C and stirred for 12 hours at 25-30°C. After completion of the reaction, reaction mixture was quenched with water and extracted into methylene chloride. The methylene chloride was distilled off from the reaction mixture under reduced pressure to get the title compound. Yield: 108 grams.
Example-11: Preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-13-dioxan-4-yl)acetamide:
A mixture of methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate (110 grams) and n-butylamine (370 grams) was heated to reflux and stirred. After completion of the reaction, the reaction mixture was distilled under reduced pressure. Water (500 ml) was added to the obtained residue followed by sodium bicarbonate and washed it with petroleum ether. The reaction mixture was extracted into methylene chloride. The solvent from the reaction mixture was distilled off under reduced pressure to get the title compound. Yield: 99 grams

Example-13: Preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide:
A mixture of tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate (10 grams), methanol (80 ml), n-butyl amine (20 ml) and potassium carbonate(10.6 grams) was heated to 40-45°C and stirred up to completion of the reaction. The reaction mixture was distilled under reduced pressure and methylene chloride (100 ml) was added to the obtained residue at 25-30°C and stirred for 15 minutes. The unwanted solid was filtered off and the filtrate was distilled off under reduced pressure to get the title compound. Yield: 7 grams
ExampIe-14: Preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2-dimethyl-13-dioxan-4-yl)acetamide:
Mixture of tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate (50 grams), methanol (300 ml) and n-butyl amine (200 ml) was heated to 60-70°C under nitrogen pressure and stirred. After the completion of the reaction, distilled off the reaction mixture completely followed by co-distillation with methylene chloride at below 55°C. Methylene chloride (500 ml) was added to the obtained residue at 25-30°C and stirred for 15 minutes. The unwanted solid was filtered off and the filtrate was distilled off under reduced pressure to get the title compound. Yield: 36 grams
Example-15: Preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2-dimethyI-l-dioxan-4-yI)acetamide:
A mixture of tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate (10 grams), methanol (80 ml), n-butyl amine (20 ml) and potassium carbonate(10.6 grams) was heated to 40-45°C and stirred up to completion of the reaction. The reaction mixture was distilled under reduced pressure and methylene chloride (100 ml) was added to the obtained residue at 25-30°C and stirred for 15 minutes. The unwanted solid was filtered off and the filtrate was distilled off under reduced pressure. The obtained residue was dissolved in methylene chloride (32 ml) and a mixture of TEMPO (0.015 grams), potassium bromide (0.36 grams) in methylene

chloride (48 ml) was added to it and stirred for 15 minutes. Sodium hypochloride solution (20.8 ml) was added to the reaction mixture at -15 to 15°C and stirred for an hour. After completion of the reaction, the reaction mixture was quenched with sodium thio sulfate solution at below 10°C. Both organic and aqueous layers were separated and aqueous layer extracted with methylene chloride. The solvent from organic layer was distilled off under reduced pressure to get the title compound. Yield: 5 grams
Example-16: Preparation of N-butyl-2-((4R,6S)-6-(hydrDxymethyl)-2,2-dimethyl-13-dioxan-4-yl)acetamide:
Mixture of tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dmiethyl-l,3-dioxan-4-yl) acetate (100 grams), methanol (1 L), n-butyl amine (200 ml) and sodium tertiary butoxide (74 grams) was heated to 40-45°C and stirred up to completion of the reaction. Distilled off the reaction mixture completely under reduced pressure and water (300 ml) was added to it at 25-30°C. The reaction mixture was cooled and acidified with aqueous acetic acid. The reaction mixture washed with cyclohexane and product from aqueous layer was extracted into methylene chloride. The organic layer was washed with saturated sodium chloride solution and the solvent from it was distilled off under reduced pressure to get the title compound. Yield: 59 grams

We Claim:
1. A process for the preparation of N-butyl-2-((4R,6S)-6-fonnyl-2,2-dimethy 1-1,3-
dioxan-4-yl)acetamide compound of formula-1,

which comprise of oxidizing the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compound of formula-5,

with suitable oxidizing agent selected from sodium hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy, free radical)/KBr or oxalyl chloride/dimethyl sulfoxide in a suitable solvent to provide N-butyl-2-((4R,6S)-6-fonnyl-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compoimd of formula-1.
2. A process for the preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-
l,3-dioxan-4-yl) acetamide compound of formula-5,

which comprise of reacting the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate of formula-2.


with n-butyl amine in methanol and in the presence or absence of a base to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5.
3. One pot process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-1,

which comprises of reacting the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate of formula-2,

with n-butyl amine in methanol and in presence or absence of a base provides the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-5,

which on in-situ oxidation with suitable oxidizing agent selected from sodium hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy, free radical)/KBr or oxalyl chloride/dimethyl sulfoxide in a suitable solvent provides N-butyl-2-((4R,6S)-6-fonnyl-2,2-dimethyl-1,3-dioxan-4-yl) acetamide compound of formula-1.

4. A process for the preparaiton of compound of formula-1, which comprises of the
following steps,
a) Reacting the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate of formula-2 with n-butyl amine in a suitable alcohol solvent like methanol in presence of a suitable alkali metal carbonates like potassium carbonate to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compoxmd of formula-5,
b) oxidizing the compound of formula-5 in-situ with suitable oxidizing agent like sodium hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy, free radical)/KBr in a suitable chloro solvents like methylene chloride to provide the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl) acetamide compound of formula-1.
5. A process for the preparation of N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-
1,3 -dioxan-4-yl)acetamide compound of formula-5,

which comprises of reacting the methyl (4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate compound of formula-4

with n-butyl amine in presence or absence of a solvent or base to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-5.

6. A process for the preparation of methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-
l,3-dioxan-4-yl)acetate compound of formula-4,

Formula-4 which comprise of reacting the 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetic acid compound of formula-S,

with dimethylsulfate in presence of a suitable base in methanol to provide methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l ,3-dioxan-4-yl)acetate compound of formula-4.
7. A process for the preparation of N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-
dioxan-4-yl)acetamide cdmpoiind of formula-1 which comprise of the following
steps;
a) Hydrolyzing the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate of formula-2

with a suitable base in a suitable solvent, provides 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetic acid compound of formula-3,


b) treating the compound of formula-3 with dimethylsulfate in presence of a suitable
base in methanol to provide methyl 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-
l,3-dioxan-4-yl)acetate compound of fonnula-4,

c) reacting the compound of formula-4 with n-butyl amine in presence or absence of
a solvent and base to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-
dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-S,

d) oxidizing the compound of formula-5 with suitable oxidizing agent selected from
sodium hypochlorite in presence of a catalyst like TEMPO (2,2,6,6-tetramethyl-l-
piperidinyloxy, free radical)/KBr or oxalyl chloride/dimethyl sulfoxide in a
suitable solvent to provide N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-
4-yl) acetamide compound of formula-1.
8. A proces for the preparation of compound of formula-1, which comprises of the following steps,
a) Hydrolyzing the tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetate of formula-2 with alkali metal hydroxides like sodium hydroxide, in a suitable polar aprotic solvent like tetrahydrofiiran provides 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3 -dioxan-4-yl) acetic acid compound of formula-3,
b) treating the compound of formula-3 with dimethylsulfate in presence of alkali metal bicarbonates like sodium bicarbonate in methanol, to provide methyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate compound of formula-4,

c) reacting the compound of formula-4 with n-butyl amine to provide N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound offormula-5,
d) oxidizing the compound of formula-5 with sodium hypochlorite in presence of TEMPO/KBr in a suitable chloro solvent like methylene chloride provides the N-butyl-2-((4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl)acetamide compound of formula-1.
9. A process for the preparation of compound of formula-1, which comprise of the following steps
a) reacting the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-dioxan-4-
yl)acetate compoimd of formula-6

with a suitable base in a methanol to provide the methyl 2-((4R,6S)-6-(hydroxy methyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-4,

b) reacting the compound of formula-4 with n-butyl amine in presence or absence of
a solvent and base to provide the N-butyl-2-((4R,6S)-6-(hydroxymethyl)-2,2-
dimethyl-l,3-dioxan-4-yl)acetamide compound of formula-S,

c) oxidizing the compound of formula-S with a suitable oxidizing agent with or
without the usage of a catalyst in a suitable solvent to provide the N-butyl-2-

((4R,6S)-6-formyl-2,2-dimethyl-l,3-dioxan-4-yl)acetainide compound of formula-1.
10. A process for the preparation of ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate compound of fonnula-6,

which comprise of the following steps;
a) Reacting the (S)-4-chloro-3-(trimethylsilyloxy)butanenitrile compound of
formula-7
with ethyl bromo acetate compoimd of formula-8

in presence of zinc dust and a suitable acid selected from methane sulfonic acid, paratoluene sulfonic acid and the like, in a polar aprotic solvent such as tetrahydrofuran to provide the (S)-ethyl 6-chloro-5-hydroxy-3-oxohexanoate compound of formula-9,

b) reducing the compound of formula-9 by treating it with diethyl methoxy borane in
presence of sodium borohydride in a suitable solvent selected from alcoholic
solvents, polar aprotic solvents or mixtures thereof, preferably mixture of solvent
such as methanol and tetrahydrofuran, to provide the (3R,5S)-ethyl 6-chloro-3,5-
dihydroxyhexanoate compound of formula-10,


c) treating the (3R,5S)-ethyl 6-chloro-3,5-dihydroxyhexanoate compound of
formula-10 with 2,2-dimethoxy propane in presence of a suitable acid suitable
acid selected from methane sulfonic acid, para toluene sulfonic acid and the like,
in a suitable ketone solvent like acetone to provide the ethyl 2-((4R,6S)-6-
(chloromethyl)-2,2-dimethyl-l,3-dioxan-4-yl)acetate compound of formula-l 1,

d) reacting the compound of formula-l 1 with sodium acetate in presence of a phase
transfer catalyst like tetrabutyl ammonium bromide, in presence or absence of a
solvent to provide the ethyl 2-((4R,6S)-6-(acetoxymethyl)-2,2-dimethyl-l,3-
dioxan-4-yl) acetate compound of formula-6.