Methylene ENYL ester KETO compounds and a metal-free catalytic process of preparation thereof

Abstract

METHYLENE ENYL ESTER KETO COMPOUNDS AND A METAL-FREE CATALYTIC PROCESS OF PREPARATION THEREOF The present invention generally relates to a field of catalysis and ligand design in organocatalytic and organometallic chemistry. Specifically, the present invention relates to use of N-Heterocyclic carbenes (NHCs) as catalysts for the metal-free Tsuji-Trost type allylation reaction of aldehydes with Morita-Baylis-Hillman adducts. More particularly, the present invention relates to compound of formula 1 representing the substituted methylene enyl ester keto compounds of formula I and substituted methylene dienyl ketone diester compounds of formula II, and process of preparation thereof. Further, the present invention relates to preparation of Sacubitril API using said compound of formula I as starting material or intermediate.

Description

[0001] METHYLENE ENYL ESTER KETO COMPOUNDS AND A METAL-FREE

[0002] CATALYTIC PROCESS OF PREPARATION THEREOF

[0003] FIELD OF THE INVENTION

[0004] The present invention relates to a compound of formula 1 representing a substituted methylene enyl ester keto compound of formula I and substituted methylene dienyl ketone diester compound of formula II. Particularly, present invention relates to a process for the preparation of the compound of formula 1. Further, the present invention relates to a process for the preparation of Sacubitril API using said compound of formula 1, 1 or II as intermediate compound.

[0005] BACKGROUND OF THE INVENTION

[0006] In the field of organic chemistry, the development of efficient and sustainable catalytic systems is of great importance. Many existing methods for the synthesis of organic compounds suffer from various limitations and disadvantages, which hinder their widespread application. These limitations include requirement of multistep processes, mandatory use of expensive and environmentally unfriendly metal catalysts (like Ni, Pd, or Pt), need for additional purification and separation steps, as well as high temperature and time requirements.

[0007] One of the challenges in organic synthesis is the efficient activation of aldehydes, which are typically less reactive due to the electrophilic nature of the carbonyl carbon. Traditional approaches often involve the use of metal catalysts to activate the aldehyde, but this not only adds complexity to the reaction process but also introduces environmental concerns and increases the cost of the synthesis.

[0008] Furthermore, the synthesis of complex organic compounds often requires multiple reaction steps, which can be time-consuming and costly. Additionally, the purification and separation of the desired products from the reaction mixture can be challenging, especially when metal catalysts are involved. These factors contribute to the need for the development of new, efficient, and environmentally friendly catalytic systems that can simplify the synthesis process and provide high yields of pure products.

[0009] In recent years, there has been a growing interest in the use of N-Heterocyclic carbenes (NHCs) as versatile catalysts in organic synthesis. NHCs have shown great potential as ligands and catalysts due to their strong nucleophilic and basic properties. Reference may be made to Journal “Organic & Biomolecular Chemistry 11.46 (2013), 7991- 7998”, which discloses umpolung of Michael acceptor (i.e. MBH adducts) carried out by NHC which was further treated with other electrophiles to afford products.

[0010] Reference may be made to Journal “Organic letters 9.13 (2007), 2581-2584”, which discloses N- heterocyclic carbene-initiated addition of a-hydroxy propargylsilanes to aldehydes for the synthesis of MBH Adducts. However, these documents do not discuss about NHCs application in the metal-free catalytic reactions. Further, methods disclosed by the above documents are complex involving multiple reaction steps.

[0011] Therefore, there is a need to provide a process that can enable simple, efficient, and metal-free reactions of aldehydes yielding novel substituted methylene enyl ester keto compounds.

[0012] OBJECTS OF THE INVENTION

[0013] Main object of present invention is to provide a substituted enyl ester keto compound of formula 1.

[0014] Another object of the present invention is to develop a metal-free catalytic approach for the efficient synthesis of substituted methylene enyl ester keto compounds of formula I.

[0015] Yet another object of the present invention is to provide a reliable and cost-effective process for the preparation of substituted methylene dienyl ketone diester compounds formula II.

[0016] Yet another object of the present invention is to enable the synthesis of Sacubitril API and related compounds using the compound of formula 1, 1 or II as starting materials or intermediates.

[0017] Yet another object of the present invention is to provide a sustainable and environmentally friendly approach to the synthesis of the compound of Formula 1 by eliminating the use of metals and reducing waste generation.

[0018] Yet another object of the present invention is to provide alternative transition metal free path for Tsuji Trost type allylation reactions.

[0019] BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Fig. 1 represents process step for the preparation of compound of formula 1 , 1 and II.

[0021] Fig. 2 represents process steps for the of preparation of Sacubitril API using said compound of formula 1 , 1 or II.

[0022] Fig. 3 represents process steps for the of preparation of Sacubitril API using said compound of formula 1 , 1 or II. SUMMARY OF THE INVENTION

[0023] Accordingly, present invention provides a compound of formula 1

[0024] Formula 1 wherein, n is 1 or 2;

[0025] A is

[0026] R, Ri and R are same or different, and are independently selected from the group consisting of hydrogen, (un)substituted alkyl (Cl to C21), (un)substituted alkoxy (Cl to C21), (un)substituted aryl (C5-C11), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un)substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether-(un)substitutedaryl, (un)substitutedalkyl-ether- (un)substitutedheteroaryl, (un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl- thio-(un)substitutedaryl, (un)substitutedalkyl-thio-(un)substitutedheteroaryl,

[0027] (un)substitutedalkyl-thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate.

[0028] In an embodiment of the present invention, compound of formula 1 is selected from compound of formula I and formula II

[0029] Formula I Formula II wherein R, R1 and R1 ’ are same as defined in claim 1.

[0030] In yet another embodiment of the present invention, said compound of formula II is selected from a group consisting of: i. Dimethyl (E)-2-(2-(4-chlorophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0031] (Ha), ii. Dimethyl (E)-2-(2-(4-bromophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0032] (Hb), iii. Dimethyl (E)-2-(2-(4-cynophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0033] (He), iv. Dimethyl (E)-2-(2-methylene-5-(2-oxo-2-phenylethylidene)hexanedioate (lid), v. Dimethyl (E)-2-(2-(4-iodophenyl)-2-oxoethylidene)-5-methylenehexanedioate (He), vi. Dimethyl (E)-2-(2-(4-(methoxycarbonyl)phenyl)-2-oxoethylidene)-5- methylenehexanedioate (Ilf), vii. Dimethyl (E)-2-(2-(4-flurophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0034] (Hg), viii. Dimethyl (E)-2-methylene-5-(2-oxo-2-p-tolyl)ethylidene) hexanedioate (Ilh), ix. dimethyl (E)-2-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0035] (Hi), x. Dimethyl (E)-2-(2-(4-hydroxyphenyl)-2-oxoethyli dene)-5 -methylenehexanedioate

[0036] (Hj), xi. Dimethyl (E)-2-(2-(3-chlorophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0037] (Hk), xii. Dimethyl (E)-2-(2-(3-bromophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0038] (HI) xiii. Dimethyl (E)-2-(2-(3-methoxyphenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0039] (Um), xiv. Dimethyl(E)-2-methylene-5-(2-oxo-2-

[0040] (3(trifluoromethoxy)phenyl)ethylidene)hexanedioate(IIn), xv. Dimethyl(E)-2-methylene-5-(2-oxo-2-(3 -(trifluoromethyl )phenyl)ethylidene) hexanedioate (IIo), xvi. Dimethyl (E)-s2-methylene-5-(2-oxo-2-(m-tolyl)ethylidene) hexanedioate (Up), xvii. Dimethyl (E)-2-methylene-5-(2-(3-nitrophenyl)-2-oxoethylidene)hexanedioate (Ilq), xviii. Dimethyl (E)-2-(2-(2-fluorophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0041] (Hr), xix. Dimethyl (E)-2-methylene-5-(2-oxo-2-(l-(phenylsulfonyl)-lH-indol-3- yl)ethylidene)hexanedioate (Ils), xx. Dimethyl (E)-2-methylene-5-(2-oxo-2-(quinolin-2-yl) ethylidene)hexanedioate (lit), xxi. Dimethyl (E)-2-methylene-5-(2-(naphthalen-2-yl)-2-oxo ethylidene)hexanedioate

[0042] (Hu), xxii. Dimethyl (E)-2-(2-(3,4-difluorophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0043] (Hv), xxiii. Dimethyl (E)-2-methylene-5-(2-oxoheptylidene) hexane -dioate (IIw), xxiv. Dimethyl (E)-2-methylene-5-(2-oxo-2-(lH-pyrrol-2-yl) ethylidene)hexanedioate

[0044] (IIx), xxv. Dimethyl (E)-2-methylene-5-(2-oxo-2-(thiophen-2-yl) ethylidene)hexanedioate

[0045] (Uy), xxvi. Dimethyl (E)-2-methylene-5-(2-oxo-2-(pyridin-2-yl)ethyli -dene)hexanedioate (Hz), xxvii. Tetramethyl 5,5'-(l,3-phenylenebis(2-oxoethan-2-yl-l-ylidene))(5E,5'E)-bis(2- methylene hexanedioate) (Ilaa), xxviii. Dimethyl (E)-2-(2-cyclopentyl-2-oxoethylidene)-5-methylenehexanedioate (Ilab), xxix. Dimethyl (E)-2-(3-methyl-2-oxobutylidene)-5-methyl-lene hexanedioate (Ilac), xxx. Diethyl (E)-2-(2-(4-chlorophenyl)-2-oxoethylidene)-5-methylenehexanedioate

[0046] (Had), xxxi. Dimethyl 3-(4-chlorobenzoyl)-2,5-dimethylene hexanedioate (Ilae), xxxii. 6-Ethyl 1 -methyl (E)-2-(2-(4-chlorophenyl)-2-oxoethyl -idene)-5- methylenehexanedioate (Ilf), and xxxiii. Dimethyl (E)-3-(4-chlorophenyl)-5-(2-(4-chlorophenyl)- 2-oxoethylidene)-2- methylenehexanedioate (Ilag).

[0047] In yet another embodiment of the present invention, said compound of formula I is selected from a group consisting of: i. Methyl 4-(4-chlorophenyl)-2-methylene-4 oxobutanoate (la), ii. Methyl 4-(4-fluorophenyl)-2-methylene-4-oxobutanoate (Id), iii. Methyl 4-(4-iodophenyl)-2-methylene-4-oxobutanoate (le), iv. Methyl 4-(4-bromophenyl)-2-methylene-4-oxobutanoate (If), v. Methyl 2-methylene-4-oxo-4-(p-tolyl)butanoate (Ig), vi. Methyl 4-(4-ethylphenyl)-2-methylene-4-oxobutanoate (Ih), vii. Methyl 4-(4-isopropylphenyl)-2-methylene-4-oxobutanoate (Ii), viii. Methyl 2-methylene-4-(4-nitrophenyl)-4-oxobutanoate (Ij), ix. Methyl 4-(4-methoxyphenyl)-2-methylene-4-oxobutanoate (Ik), x. Methyl 4-(4-hydroxyphenyl)-2-methylene-4-oxobutanoate (II), xi. Methyl 4-(3-chlorophenyl)-2-methylene-4-oxobutanoate (Im), xii. Methyl 4-(3-bromophenyl)-2-methylene-4-oxobutanoate (In), xiii. Methyl 4-(3-methoxyphenyl)-2-methylene-4-oxobutanoate (Io), xiv. Methyl 2-methylene-4-oxo-4-(3-(trifluoromethoxy)phenyl) butanoate (Ip), xv. Methyl 2-methylene-4-oxo-4-(3-(trifluoromethyl)phenyl) butanoate (Iq), xvi. Methyl 2-methylene-4-oxo-4-(m-tolyl)butanoate (Ir), xvii. Methyl 4-(furan-2-yl)-2-methylene-4-oxobutanoate (Is), xviii. Methyl 2-methylene-4-oxo-4-(thiophen-2-yl)butanoate (It), xix. Methyl 2-methylene-4-oxo-4-(lH-pyrrol-2-yl)butanoate (lu), xx. Methyl 2-methylene-4-oxo-4-(l-(phenylsulfonyl)-lH-pyrrol-2-yl)butanoate (Iv), xxi. Methyl 2-methylene-4-oxo-4-(pyridin-2-yl)butanoate (Iw), xxii. Methyl 2-methylene-4-oxo-4-(quinolin-2-yl)butanoate (ly), xxiii. Methyl 2-methylene-4-oxo-4-(pyridin-3-yl)butanoate (Iz), xxiv. Methyl 4-(2-fluorophenyl)-2-methylene-4-oxobutanoate (laa), xxv. Methyl 4-(lH-indol-3-yl)-2-methylene-4-oxobutanoate (lab), xxvi. Methyl 2-methylene-4-oxo-4-(l-(phenylsulfonyl)-lH-indol-3-yl)butanoate (lac), xxvii. Methyl 4-(benzo[d][l,3]dioxol-5-yl)-2-methylene-4-oxo butanoate (lad), xxviii. Methyl 4-(5-bromo-lH-indol-3-yl)-2-methylene-4-oxo butanoate (lae), xxix. Methyl 4-(ferrocene)-2-methylene-4-oxobutanoate (laf), xxx. Dimethyl 4,4'-(l,3-phenylene)bis(2-methylene-4-oxobutanoate) (lag), xxxi. Methyl 2-methylene-4-oxo-5-phenylpentanoate (lah), xxxii. Methyl 4-(3,4-difluorophenyl)-2-methylene-4-oxo butanoate (lai), xxxiii. Methyl 5-([l,l'-biphenyl]-4-yl)-2-methylene-4-oxo butanoate (laj), xxxiv. Methyl 2-methylene-4-oxononanoate (lak), xxxv. Methyl 2-methylene-4-oxopentanoate (lam), and xxxvi. Methyl 4-cyclopentyl-2-methylene-4-oxobutanoate (Ian).

[0048] In yet another embodiment, present invention provides a process for the preparation of compounds of formula 1 as claimed in claim 1, wherein said process comprising the steps of: a) carrying out reaction of substituted aldehyde of formula A with substituted Morita- Baylis-Hillman adducts of formula B in presence of N-Heterocyclic carbene (NHCs) as formula C as catalyst, organic or inorganic base and solvent at a temperature in the range of 30-70 °C for a time period in the range of 0.5 to 20 hr to obtain the said compound of formula I of Formula 1 and crude of formula II of Formula 1 respectively; wherein R, Ri and Rf are same as defined in claim 1 or 2;

[0049] R2, R3 and R4 are independently selected from the group consisting of C1-C6 (un)substituted alkyl, C1-C6 (un)substituted cycloalkyl, and (un)substituted aryl; and b) treating the crude of formula II of Formula 1 obtained in step a) with solvent at a temperature in the range of 65-75°C and for a time period in the range of 6-7 h to obtain compound of formula II of Formula 1.

[0050] In yet another embodiment of the present invention, N-heterocyclic carbenes (NHCs) catalyst is selected from the group consisting of

[0051] In yet another embodiment of the present invention, the solvent used is selected from a group consisting of dichloromethane (DCM), acetonitrile (ACN), dimethylformamide (DMF), toluene, 1,4-dioxane, 1 ,2-dichloroethane (DCE), dimethyl sulfoxide (DMSO), Heptane, o-xylene, Chlorobenzene, Cyclohexane, Diethyl ether, Isopropyl alcohol, Chloroform, tetrahydrofuran, hexafluro-2-propanol, o-dichlorobenzene, isoamyl alcohol, n-propyl alcohol, Acetone, Ethyl Acetate, Dimethyl acetamide, ethyl methyl ketone, MTBE, methanol, N-methyl morpholine, N- methyl pyrrolidone, water, carbon tetrachloride, 1,1, 2, 2 tetrachloroethane or mixture thereof.

[0052] In yet another embodiment of the present invention, the inorganic base used for the preparation of compound of formula I, and the organic base is used for the preparation of compound of formula II; wherein the inorganic base is selected from cesium carbonate, sodium carbonate, potassium carbonate, sodium butoxide, sodium hydride, and 4-dimethylaminopyridine; and wherein the organic base is selected from l,4-diazabicyclo[2.2. 2]octane (DABCO), 4- dimethylaminopyridine, 1,8-Diazabicyclo 5.4.0 undec-7-ene (DBU), dimethylacetamide (DMA), and pyridine.

[0053] In yet another embodiment, present invention provides a process of preparation of sacubitril using said compound of formula 1, I or II as claimed in claim 1 or 2, wherein said process comprises steps of: a) mixing and reacting the compound of formula 1, I or II being an intermediate compound in methanol in presence of catalyst Pd / Carbon under stirring and hydrogen gas at temperature in the range of 25-35 °C for time period in the range of 1.5-2.5 h to obtain a crude mixture; b) dissolving the crude mixture as obtained in step a) directly without purifying in methanol, cooling to temperature of -40 °C followed by reacting with sodium borohydride as reducing agent for time period in the range of 1.5-3.5 h to obtain intermediate compound 6; c) dissolving the intermediate compound 6 as obtained in step b) in dichloromethane followed by reacting with dropwise addition of methane sulfonyl chloride in presence of triethylamine as base and 4-(dimethylamino)pyridine as catalyst under stirring at temperature in the range of 0-2 °C for time period in the range of 1.5-2.5 h to obtain crude mesylate mixture; d) reacting said crude mesylate mixture as obtained in step c) with sodium azide in presence of dimethyl formamide as solvent at temperature in the range of 50-70 °C for time period in the range of 5-7 h to obtain intermediate compound 8 in the form of diastereomers 8a and 8b; e) mixing and reacting the intermediate compound 8a as obtained in step d) with triphenylphosphine in presence of chloroform as solvent under stirring at temperature in the range of 25-35 °C to obtain a solution mixture; f) adding triethyl amine and succinic anhydride sequentially in the solution mixture as obtained in step e) and reacting under reflux for time period in the range of 3-5 h to obtain the sacubitril.

[0054] In yet another embodiment, present invention provides a process of preparation of sacubitril using said compound of formula 1, 1 or II comprises steps of: a) mixing and reacting the compound of formula 1, I or II being an intermediate compound in methanol and cooled down to temperature of -40 °C followed by reacting with sodium borohydride as reducing agent for time period in the range of 3-5 h to obtain intermediate compound 7 ; b) reacting said intermediate compound 7 as obtained in step a) with sodium azide in presence of dimethyl formamide as solvent at temperature in the range of 50-70 °C for time period in the range of 5-7 h to obtain intermediate compound 9; c) mixing and reacting the intermediate compound 9 as obtained in step b) with triphenylphosphine in presence of chloroform as solvent under stirring at temperature in the range of 25-35 °C to obtain a solution mixture; d) adding triethyl amine and succinic anhydride sequentially in the solution mixture as obtained in step c) and reacting under reflux for time period in the range of 3-5 h to obtain intermediate compound 10; e) mixing and reacting the intermediate compound 10 as obtained in step (d) in methanol in presence of catalyst Pd / Carbon under stirring and hydrogen gas at temperature in the range of 25-35 °C for time period in the range of 1.5-2.5 h to obtain sacubitril.

[0055] DETAILED DESCRIPTION OF THE INVENTION “Alkyl” as used herein is collection of carbon atoms that are covalently linked together in normal, secondary, tertiary or cyclic arrangements, i.e., in linear, branched, cyclic arrangement or some combination thereof. An alkyl substituent to structure is chain of carbon atoms that is covalently attached to structure through sp3carbon of substituent. The alkyl substituents, as used herein, contains one or more saturated moieties or groups and may additionally contain unsaturated alkyl moieties or groups, i.e., substituent may comprise one, two, three or more independently selected double bonds or triple bonds of combination thereof, typically one double or

[0056] Cycloalkyl as used here is a monocyclic, bicyclic or tricyclic ring system composed of only carbon atoms. The term “cycloalkyl” encompasses a monocyclic or polycyclic aliphatic, nonaromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. The number of carbon atoms in an cycloalkyl substituent, moiety or group can vary and typically is 3 to about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C3. 8 alkyl or C3-C8 alkyl means an cycloalkyl substituent, moiety or group containing 3, 4, 5, 6, 7 or 8 carbon atoms.

[0057] “Alkylamine” as used herein means an — N(alkyl)xHygroup, moiety or substituent where x and y are independently selected from the group x=l, y=l and x=2, y=0. Alkylamine includes those — N(alkyl)xHygroups wherein x=2 and y=0 and the alkyl groups taken together with the nitrogen atom to which they are attached form a cyclic ring system.

[0058] “Heteroalkylene” as used herein means alkylene (i.e. alkanediyl) group, moiety or substituent in which one or more skeletal atoms of alkyl are selected from atom other than carbon, e.g. oxygen, nitrogen, sulfur, phosphorus or combinations thereof. Heteroalkylene includes Ci- Ce heteroalkylene or C1-C4 heteroalkylene. Exemplary heteroalkylenes include, but are not limited to — OCH2— , — OCH(CH3)— , — OC(CH3)2— , — OCH2CH2— , — CH2O— , — CH(CH3)O— , C(CH3)2O— , — CH2CH2O— , — CH2OCH2— , — CH2OCH2CH2— , — CH2CH2OCH2— , — SCH2— , etc.

[0059] “Alkenyl” as used herein means a substituent, moiety or group that comprises one or more double bond moities (e.g., — CH=CH — ) or 1, 2, 3, 4, 5 or 6 or more, typically 1, 2 or 3 such moieties and can include an aryl moiety or group such as benzene, and additionally comprises linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof unless the alkenyl moiety is a vinyl moiety (e.g., — CH=CH2). An alkenyl moiety, group or substituent with multiple double bonds may have the double bonds arranged contiguously (i.e. a 1, 3 butadienyl moiety) or non-contiguously with one or more intervening saturated carbon atoms or a combination thereof, provided that a cyclic, contiguous arrangement of double bonds do not form a cyclically conjugated system of 4n+2 electrons (i.e., aromatic). The number of carbon atoms in an alkenyl group or moiety can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C2-8 alkenyl or C2-8 alkenyl means an alkenyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms and C2-6 alkenyl or C2-6 alkenyl means an alkenyl moiety containing 2, 3, 4, 5 or 6 carbon atoms.

[0060] “Alkynyl” as used herein means substituent, moiety or group that comprises one or more triple bond moieties (i.e., — C=C — ) e.g., 1, 2, 3, 4, 5, 6 or more, typically 1 or 2 triple bonds, optionally comprising 1, 2, 3, 4, 5, 6 or more double bonds, with remaining bonds (if present) being single bonds and comprising linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof, unless the alkynyl moiety is ethynyl. The number of carbon atoms in an alkenyl moiety or group can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C2-8 alkynyl or C2-8 alkynyl means an alkynyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms.

[0061] “Aromatic” as used herein refers to a planar ring having a delocalized pi-electron system containing 4n+2 pi electrons, where n is a positive integer. Aromatic rings can be formed from five, six, seven, eight, nine, ten, or more than ten atoms. Aromatics are optionally substituted. The term “aromatic” includes both carboxcylic aryl (“aryl”, e.g., phenyl) and heterocyclic aryl (or “heteroaryl” or “heteroaromatic”) groups (e.g., pyridine).

[0062] “Aryl” as used here means an aromatic ring system or a fused ring system with no ring heteroatoms comprising 1, 2, 3 or 4 to 6 rings, typically 1 to 3 rings, wherein the rings are composed of only carbon atoms; and refers to a cyclically conjugated system of 4n+2 electrons (Huckel rule), typically 6, 10 or 14 electrons some of which may additionally participate in exocyclic conjugation (cross-conjugated (e.g., quinone). Aryl substituents, moieties or groups are typically formed by five, six, seven, eight, nine, or more than nine, carbon atoms. Aryl substituents, moieties or groups are optionally substituted. Exemplary aryls include Ce-Cio aryls such as phenyl and naphthalenyl and phenanthryl. Depending on the structure, an aryl group can be a monoradical or a diradical (i.e., an arylene group).

[0063] “Arylalkyl” as used herein means a substituent, moiety or group where an aryl moiety is bonded to an alkyl moiety, i.e., -alkyl-aryl, where alkyl and aryl groups are as described above, e.g., — CH2— C6H5or — CH2CH(CH3)— C6H5. “Substituted alkyl”, “substituted cycloalkyl”, “substituted alkenyl”, “substituted alkynyl”, substituted alkylaryl”, “substituted arylalkyl”, “substituted heterocycle”, “substituted aryl” and the like as used herein mean alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl heterocycle, aryl or other group or moiety as defined or disclosed herein that has substituent(s) that replaces hydrogen atom(s) or substituent(s) that interrupts carbon atom chain. Alkenyl and alkynyl groups that comprise substituent(s) are optionally substituted at carbon that is one or more methylene moieties removed from double bond.

[0064] “Optionally substituted” covers “Optionally substituted alkyl”, “optionally substituted alkenyl”, “optionally substituted alkynyl”, “optionally substituted alkylaryl”, “optionally substituted arylalkyl”, “optionally substituted heterocycle”, “optionally substituted aryl”, “optionally substituted heteroaryl”, “optionally substituted alkylheteroaryl”, “optionally substituted heteroarylalkyl” and the like as used herein mean an alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl heterocycle, aryl, heteroaryl, alkylheteroaryl, heteroarylalkyl, or other substituent, moiety or group as defined or disclosed herein that has a substituent(s) that optionally replaces hydrogen atom(s) or substituent(s) that interrupts carbon atom chain.

[0065] “Heterocycle” or “heterocyclic” as used herein means a cycloalkyl or aromatic ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms comprising the ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically N, O or S wherein two or more heteroatoms may be adjacent to each other or separated by one or more carbon atoms, typically 1-17 carbon atoms, 1-7 atoms or 1-3 atoms. Heterocycles include heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings (also known as heteroalicyclic groups) containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 4 to 10 atoms in its ring system, and with the proviso that the any ring does not contain two adjacent O or S atoms.

[0066] “Heteroaryl” as used herein means an aryl ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms comprising the aryl ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically, oxygen ( — O — ), nitrogen ( — NX — ) or sulfur ( — S — ) where X is — H, protecting group or Ci -6 optionally substituted alkyl, wherein heteroatom participates in conjugated system either through pi- bonding with adjacent atom in ring system or through lone pair of electrons on heteroatom and may be optionally substituted on one or more carbons or heteroatoms, or combination of both, in manner which retains cyclically conjugated system. Examples of heteroaryls include by way of example and not limitation pyridyl, thiazolyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, purinyl, imidazolyl, benzofuranyl, indolyl, isoindoyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridazinyl, pyrazinyl, benzothiopyran, benzotriazine, isoxazolyl, pyrazolopyrimidinyl, quinoxalinyl, thiadiazolyl, triazolyl and the like. Heterocycles that are not heteroaryls include, by way of example and not limitation, tetrahydrothiophenyl, tetrahydrofuranyl, indolenyl, piperidinyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, piperazinyl, quinuclidinyl, morpholinyl, oxazolidinyl and the like.

[0067] “Heterocycloalkyl” or “heteroalicyclic” as used herein means cycloalkyl group or substituent wherein at least on carbon of cycloalkyl chain is replaces with heteroatom selected from nitrogen, oxygen and sulfur. The heterocycloalkyl may be fused with aryl or heteroaryl. Heterocycloalkyl includes, by way of example and not limitation, oxazolidinonyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, and indolinyl. Heteroalicyclics further includes all ring forms of carbohydrates, including but not limited to monosaccharides, disaccharides and oligosaccharides. Typically, heterocycloalkyl is C2-C10 heterocycloalkyl and includes C4- C 10 heterocycloalkyl. Heterocycloalkyl may contain 0-2 N atoms, 0-2 O atoms or 0-1 S atoms. “Heteroarylalkyl” as used herein means a substituent, moiety or group where a heteroaryl moiety is bonded to an alkyl moiety, i.e., -alkyl-heteroaryl, where alkyl and heteroaryl groups are as described above. When heteroarylalkyl is used as a Markush group (i.e., a substituent) the alkyl moiety of the heteroarylalkyl is attached to a Markush formula with which it is associated through a sp3carbon of the alkyl moiety.

[0068] “Alkylheteroaryl” as used herein means substituent, moiety or group where heteroaryl moiety is bonded to alkyl moiety, i.e., heteroaryl-alkyl, where heteroaryl and alkyl groups are as described above. When heteroarylalkyl is used as Markush group (substituent), heteroaryl moiety of heteroarylalkyl is attached to Markush formula with which it is associated through sp2carbon or heteroatom of alkyl moiety.

[0069] “Halogen” or “halo” as used herein means fluorine, chlorine, bromine or iodine.

[0070] “Haloalkyl” as used herein means an alkyl substituent moiety or group in which one or more of its hydrogen atoms are replaced by one or more independently selected halide atoms. Haloalkyl includes Ci-C4haloalkyl. Example but non-limiting Ci-C4haloalkyls are — CH2CI, CJEBr, — CH2I, — CHBrCl, — CHC1 — CH2CI and — CHC1 — CH2I. “Haloalkylene” as used herein means an alkylene substituent, moiety or group in which one or more hydrogen atoms are replaced by one or more halide atoms. Haloalkylene includes Ci-Cehaloalkylenes or Ci-C4haloalkylenes. “Ester” as used herein means a substituent, moiety or group that contains a — C(O) — O — structure (i.e., ester functional group) wherein the carbon atom of the structure is not directly connected to another heteroatom and is directly connected to — H or another carbon atom.

[0071] “Acetal”, “thioacetal”, “ketal”, “thioketal” and the like as used herein means a moiety, group or substituent comprising or consisting of a carbon to which is bonded two of the same or different heteroatoms wherein the heteroatoms are independently selected S and O.

[0072] “Ether” as used herein means an organic moiety, group or substituent that comprises or consists of 1, 2, 3, 4 or more — O — moieties, usually 1 or 2, wherein no two — O — moieties are immediately adjacent (i.e., directly attached) to each other, group.

[0073] “Carbonate” as used here means a substituent, moiety or group that contains a — O — C(=O) — O — structure (i.e., carbonate functional group). Typically, carbonate groups as used here comprise or consist of an organic moiety containing 1-50 carbon atoms, 1-20 carbon atoms or 1- 8 carbon atoms and 0 to 10 independently selected heteroatoms (e.g., O, S, N, P, Si), typically 0- 2, bonded through the — O — C(=O) — O — structure, e.g., organic moiety-0 — C(=O) — O — .

[0074] “Carbamate” or “urethane” as used here means a substituent, moiety or group that contains a — O — C(=O)N(RPR) — , — O — C(=O)N(RPR)2, — O — C(=O)NH(optionally substituted alkyl) or — O — C(=O)N (optionally substituted alkyl)2- structure (i.e., carbamate functional group) where RPRand optionally substituted alkyl are independently selected and RPRare independently — H, a protecting group or an organic moiety as described for ester, alkyl or optionally substituted alkyl.

[0075] As used herein, the term “alkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group. Examples of alkylene groups include, but are not limited to, ethan-l,2-diyl, propan- 1,3-diyl, propan- 1,2-diyl, butan-l,4-diyl, bu tan- 1,3 -diyl, butan-l,2-diyl, 2-methyl-propan-l,3-diyl, and the like.

[0076] As used herein, the term “alkoxy”, employed alone or in combination with other terms, refers to a group of formula — O-alkyl, wherein the alkyl group as defined above. Example alkoxy groups include but not limited to methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy, and the like. As used herein, the term “alkylamino” refers to a group of formula — NH(alkyl), wherein the alkyl group is as defined above. As used herein, the term “alkoxycarbonyl” refers to a group of formula — C(O)O-alkyl, wherein the alkyl group is as defined above. As used herein, the term “alkylcarbonyl” refers to a group of formula — C(O)-alkyl, wherein the alkyl group is as defined above. As used herein, the term “alkylcarbonylamino” refers to a group of formula — NHC(O)- alkyl, wherein the alkyl group is as defined above. As used herein, the term “alkylsulfonylamino” refers to a group of formula — NHS(O)2-alkyl, wherein the alkyl group is as defined above. As used herein, the term “aminosulfonyl” refers to a group of formula — S(O)2NH2. As used herein, the term “thio” refers to a group of formula — SH. As used herein, the term “alkylthio” refers to a group of formula — S-alkyl, wherein the alkyl group is as defined above. As used herein, the term “amino” refers to a group of formula — NH2. As used herein, the term “carbamyl” to a group of formula — C(0)NH2. As used herein, the term “carbonyl”, employed alone or in combination with other terms, refers to a — C(O) — group. As used herein, the term “carboxy” refers to a group of formula — C(O)OH. As used herein, “haloalkoxy” refers to a group of formula — O-haloalkyl where alkyl and halo / halogen is as defined above. An example haloalkoxy group is OCF3. In some embodiments, the haloalkoxy group is fluorinated only.

[0077] The expressions, “ambient temperature” and “room temperature” or “rt” as used herein, are understood in the art, and refer generally to a temperature, e.g. a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20° C to about 30° C.

[0078] The present invention allows for the direct synthesis of desired compounds from aldehydes and Morita-Baylis-Hillman adducts in a simple one or two-step process. By eliminating the need for metal catalysts and reducing the number of reaction steps, the process provided by the present invention has the potential to overcome the limitations and disadvantages of existing methods, making the synthesis of organic compounds more efficient, sustainable, and cost-effective.

[0079] The present invention relates to a compound of formula 1

[0080] Formula 1 wherein, n is 1 or 2;

[0081] R, Ri and R are same or different, and are independently selected from hydrogen, (un)substituted alkyl (Cl to C21), (un)substituted alkoxy (Cl to C21), (un)substituted aryl (C5- Cl l), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un)substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether-(un)substitutedaryl, (un)substitutedalkyl-ether-

[0082] (un)substitutedheteroaryl, (un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl- thio-(un)substitutedaryl, (un)substitutedalkyl-thio-(un)substitutedheteroaryl,

[0083] (un)substitutedalkyl-thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate.

[0084] The present invention relates to the compound of formula 1 is selected from substituted methylene enyl ester keto compounds of formula I and / or substituted methylene dienyl ketone diester compounds of formula II wherein R, Ri and Rf are same as defined above.

[0085] The present invention relates to a process of preparation of compounds of formula I and / or II of compound of formula 1, comprising the steps of: a) reacting substituted aldehyde of formula A with substituted Morita-Baylis-Hillman adducts of formula B in presence of NHC as catalyst of formula C, organic or inorganic base and solvent at a temperature in the range of 30-70 °C for a time period in the range of 0.5 to 20 hr to obtain said compound of formula 1 or formula I, wherein the compound of formula A, formula B, and N-Heterocyclic carbenes (NHCs) as formula C are represented as: wherein R, Ri and Rf are same as defined above;

[0086] R2, R3 and R4 are selected from the group consisting of C1-C6 (un) substituted alkyl, Cl- C6 (un) substituted cycloalkel, (un) substituted aryl; and b) treating the compound obtained in step a) with solvent at a temperature in the range of 65 -75 °C and for a time period in the range of 6-7 h to obtain compound of formula 1 or formula II.

[0087] In general following representative NHCs we have used,

[0088] The preparation of compounds of formula I includes reaction of substituted aldehyde of formula A (1.5 eq) with substituted Morita-Baylis-Hillman adducts of formula B (1 eq) in presence of 2- 20 mol% NHC as catalyst, 5-40 mol% inorganic base and solvent at temperature ranging from 20-45°C for time period of 1 -20 hours under the inert atmosphere.

[0089] The preparation of compounds of formula II includes reaction of substituted aldehyde of formula A (1 eq) with substituted Morita-Baylis-Hillman adducts of formula B (2 eq.) in presence of 2- 20 mol% NHC as catalyst, 5-40 mol% Organic base, and solvent at temperature ranging from 20-45°C for time period of 1-20 hours under the inert atmosphere to obtain given compound mixtures of formula II and its intermediate (Z), which are further heated in solvent at a temperature of 50°C-refiux and for time period 2-20 hours to completely obtain compounds of formula II; wherein the compound of formula A, formula B, NHCs as formula C and intermediate formula Z are represented as: wherein R, Ri, R , R2, R3, and R4 are same as defined above.

[0090] For the preparation of formula I, the base used in step a) is the inorganic base, and for the preparation of formula II, the base is organic base.

[0091] The solvent used in the process for preparation of the compound of formula I and the compound of formula II is selected from a group consisting of dichloromethane (DCM), acetonitrile (ACN), dimethylformamide (DMF), toluene, 1,4-dioxane, 1 ,2-dichloroethane (DCE), dimethyl sulfoxide (DMSO), Heptane, o-xylene, Chlorobenzene, Cyclohexane, Diethyl ether, Isopropyl alcohol, Chloroform, tetrahydrofuran, hexafluro-2-propanol, o-dichlorobenzene, isoamyl alcohol, n- propyl alcohol, Acetone, Ethyl Acetate, Dimethyl acetamide, ethyl methyl ketone, MTBE, methanol, N-methyl morpholine, N- methyl pyrrolidone, water, carbon tetrachloride, 1,1, 2, 2 tetrachloroethane or mixture thereof.

[0092] The process of preparation of compounds of formula I and II provided by the present invention provide yield varying from 35% to 88% for compound of formula I and yield varying from 35% to 81 % for compound of formula II as this protocol involves three consecutive reactions steps (NHC catalysed Tsuji- Trost type allylation reaction, Michael addition reaction of intermediate with one more mole of MBH adduct and 3,3-Sigmatropic rearrangement reaction.)

[0093] The present invention relates to a process of preparation of Sacubitril API using said compound of formula 1, 1 or II is described in Fig. 2; wherein the synthetic procedure is new up to synthesis of compound 8. The last step (from compound 8 to compound 11) is reported in the literature e.g. Kaur, A.; Gehlawat, A.; Prakash, R.; Pandey, S. K. Enantioselective Total Synthesis of Sacubitril. Chemistry Select, 2021, 6(33), 8928-8930. The present invention relates to a process of preparation of Sacubitril API using said compound of formula 1, I or II is shown in Fig. 3; wherein the synthetic procedure provided above is new up to synthesis of compound 9. The last two steps in route a (from compound 9 to compound 11) or last step in route b (from compound 9 to compound 11) is reported in the literature e.g. Liu, K. K.-C.; Sakya, S. M.; O’Donnell, C. J.; Flick, A. C.; Li, J. Synthetic Approaches to the 2009 New Drugs. Bioorg. Med. Chem. 2011, 19, 1136-1154.

[0094] EXAMPLES

[0095] Following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.

[0096] Example 1: General procedure for the synthesis of Compound of formula I

[0097] Reaction of substituted aldehyde of formula A (1.5 eq) with substituted Morita-Baylis-Hillman adducts of formula B (1 eq) in presence of NHC as catalyst (2-20 mol%), Inorganic base (5-40 mol%) and solvent (0-2ml) at specific temperature (20-45°C) for time period of 1-20 hrs under the inert atmosphere to obtain given compounds of formula I.

[0098] Experimental procedure for synthesis of compound with formula lb

[0099] An oven dried schlenk tube equipped with a magnetic stir bar was charged with NHC-C2 (10.57 mg, 0.0284 mmol, 15 mol%) and CS2CO3 base (18.54 mg, 0.0568 mmol, 30 mol%). Reaction vessel was evacuated and backfilled with Argon for three times. Under an argon atmosphere methyl 2-(((tert-butoxycarbonyl)oxy)methyl)acrylate (41 mg, 0.1846 mmol, 1 eq.) benzaldehyde (30.18 mg, 0.2844 mmol, 1.5 eq), and 1,4-Dioxane (0.1 mL) were added successively and the tube was tightly closed with the glass stopper. The resulting mixture was kept for stirring at room temperature for 90 min. After completion of reaction by TLC, ethyl acetate added to reaction mixture and organic phase was washed with IN HC1 (15 mL), saturated NaHCCh solution (15 mL) and brine (15 mL). The combined organic phase was then dried over Na2SC>4 and filtered. The residue was purified by column chromatography over 230-400 flash silica gel (PE: EtOAc = 96:5) to give the desired product lb (64% yield).

[0100] Compounds of formula I prepared using the process given above along with their characterization data

[0101] Example 2: General procedure for the synthesis of Compound of formula II

[0102] Reaction of substituted aldehyde of formula A (1 eq) with substituted Morita-Baylis-Hillman adducts of formula B (2 eq.) in presence of NHC as catalyst (2-20 mol%), Organic base (5-40 mol%), and solvent (0-2ml) at specific temperature (20-45°C) for time period of 1-20 hrs under the inert atmosphere to obtain given compound mixture of formula I and its intermediate which was further heated in solvent (0-2ml) at a temperature range 50°C-reflux and for time period 2- 20 hrs to completely obtain compounds of formula II.

[0103] Experimental procedure for synthesis of compound with formula Hb

[0104] An oven dried schlenk tube equipped with a magnetic stir bar was charged with 4- bromobenzaldehyde (30mg, 0.1621 mmol, leq) and methyl 2-(((tert- butoxycarbonyl)oxy)methyl)acrylate (70.1 mg, 0.3242 mmol, 2 eq.) Reaction vessel was evacuated and backfilled with argon for three times. Under an argon atmosphere, NHC-C3 (10.06 mg, 0.0243 mmol, 15 mol%), DMAP base (7.92 mg, 0.0648 mmol, 40 mol%) and toluene (0.6 mL) were added successively and the tube was tightly closed with the glass stopper. The resulting mixture was stirred at room temperature for 30 min. After that ethyl acetate added to the reaction mixture and organic phase was washed with 1 N HC1 (15 mL), saturated NaHCCL solution (15 mL) and brine (15 mL). The combined organic phase was then dried over Na2SC>4 and filtered. The filtrate concentrated under vacuum to remove all volatiles. Further, toluene (0.6 mL) was added to the crude reaction mixture and kept for stirring in a preheated oil-bath at 70°C for 6h. After cooling to room temperature, residue was purified by column chromatography over 230- 400 flash silica gel (PE: EtOAc = 96:4) to give the desired product lib (66% yield).

[0105] Characterization Data of Compounds of Formula II

[0106] Example 3: Procedure for the synthesis of Sacubitril and / or their analogues using compound of formula I as intermediate compound a) Synthesis of methyl 5-([l,l'-biphenyl]-4-yl)-2-methylene-4-oxopentanoate (Route A) The compound (3af) prepared according to the same procedure as described in Experimental procedure for synthesis of compound with formula lb. Methyl 5-([l,l'-biphenyl]-4-yl)-2- methylene-4-oxopentanoate (3af) as yellow oil with 36% yield isolated yield, Rf = 0.18 in 10% EtOAc:Pet ether.

[0107] 'H NMR (400 MHz, CDC13): 8 ppm 7.61 - 7.56 (m, 4 H), 7.48 - 7.42 (m, 2 H), 7.38 - 7.33 (m, 1 H), 7.31 (d, J = 8.3 Hz, 2 H), 6.39 - 6.33 (m, 1 H), 5.63 (d, J = 0.9 Hz, 1 H), 4.20 (q, J = 7.1

[0108] Hz, 2 H), 3.84 (s, 2 H), 3.48 (s, 2 H), 1.28 (t, J = 1.2 Hz, 3 H).13C NMR (101 MHz, CDCI3): 8 ppm 204.8, 166.3, 140.7, 140.1, 134.4, 133.0, 130.0, 128.8, 128.7, 127.5, 127.3, 127.1, 61.1, 49.5, 45.1, 14.1. HRMS (ESI) m / z calcd for C20H20O3 [M+H]+: 309.1485, found: 309.1483. Route B: An oven-dried schlenk tube equipped with a magnetic stir bar was charged with NHC- C3 (63.3mg, 0.15 mmol, 0.15 equiv.). The reaction vessel was evacuated and backfilled with argon three times. Under an argon atmosphere, 4,4’-Biphenyl Acetaldehyde(200 mg, 1.02 mmol, 1 equiv.) and 2-(((tert-butoxycarbonyl)oxy)ethyl)acrylate (234.6 mg, 1.02 mmol, 1 equiv.) were added followed by DCE (0.6 mL). After getting clear solution, DMAP (37.35 mg, 0.31 mmol, 0.3 equiv.) was added and the tube was tightly closed with glass stopper. The resulting mixture was stirred at room temperature. After 30 min, ethyl acetate was added to the reaction mixture, and the organic phase was washed with 1 N HC1 (15 mL), saturated NaHCCh solution (15 mL), and brine (15 mL). The combined organic phase was dried over Na2SC>4 and filtered. The filtrate was concentrated under vacuum to remove all volatiles. The residue was purified by column chromatography using (1:9 EtOAc : Pet ether) over 230-400 flash silica gel to afford methyl 5- ([l,l'-biphenyl]-4-yl)-2-methylene-4-oxopentanoate (3af) as yellow oil with 59% yield (185.42 mg). b) Synthesis of ethyl-5-([l,l'-biphenyl]-4-yl)-4-hydroxy-2-methylpentanoate (6)

[0109] To a solution of 3af (200 mg, 0.65 mmol) in MeOH (2 mL), catalytic Pd / Carbon was added and the resulting mixture was stirred under H2 atmosphere for 2 h. After complete consumption of the starting material, the reaction mixture was filtered through a pad of celite and concentrated under reduced pressure. The crude product obtained was used in the next step without purification. The crude reduced derivative was dissolved in MeOH (5 mL) and cooled to -40 °C, to this cooled reaction mixture NaBH4 (1.2 equiv.) was added and stirred at the same temperature for 2 h. After complete consumption of the starting material by TLC, the reaction was quenched by 1 mL AcOH. Volatiles were removed under vacuo and residue was dissolved in DCM followed by washing with brine. The residue was purified by column chromatography using (1:9 EtOAc: Pet ether) over 230-400 flash silica gel to afford ethyl-5-([l,l'-biphenyl]-4-yl)-4- hydroxy-2-methylpentanoate (6) as a colorless oil with 92% yield,

[0110] Rf= 0.34 in 20% EtOAc:Pet ether. 'H NMR (400 MHz, CDCI3): 8 ppm 7.57 (m, 4 H), 7.45 (t, 7 = 7.6 Hz, 2 H), 7.36 (m, 1 H), 7.30 (d, J = 8.1 Hz, 2 H), 4.15 (q, 7 = 7.1 Hz, 2 H), 3.92 (m, 1 H), 2.91 - 2.82 (m, 1 H), 2.82 - 2.63 (m, 2 H), 1.97 (m, 1 H), 1.64 (m, 1 H), 1.29 - 1.25 (t, 7= 7.1 Hz, 3 H), 1.24 - 1.19 (d, 7 = 7 Hz, 3 H).13C NMR (101 MHz, CDCI3): 8 ppm 177.3, 140.9, 139.5, 137.3, 129.9, 128.8, 127.3, 127.2, 127.0, 71.1, 60.5, 44.2, 40.5, 37.0, 17.3, 14.2. HRMS (ESI) m / z calcd for C20H25O3 [M+H]+: 313.1798, found: 313.1797. c) Synthesis of ethyl-5-([l,l'-biphenyl]-4-yl)-4-azido-2-methylpentanoate (8)

[0111] To a stirred solution of alcohol 6 (270 mg, 0.86 mmol, 1 equiv.) in dry DCM (5 mL) at 0 °C, triethylamine (437 mg, 4.32 mmol, 5 equiv.), and a catalytic amount of DMAP (10.56 mg, 0.09 mmol, 0.1 equiv.) were added followed by dropwise addition of methane sulfonyl chloride (198.15 mg, 1.73 mmol, 2 equiv.). The stirring was continued for 2 h at 0 °C. After completion of the reaction, the reaction mixture was quenched with saturated aqueous Na2COs and partitioned between brine and CH2CI2. The organic extract was dried over Na2SC>4, and concentrated in vacuo. The mesylate derivative thus obtained was further used in the next reaction without purification. The above-mesitylated derivative and NaNa (67.46 mg, 1.04 mmol, 1.2 equiv.) were dissolved in dry DMF (5 mL) and the resultant solution was stirred at 60 °C for 6 h. After completion of the reaction, monitored by using TLC, the mixture was diluted with EtOAc, washed with water and brine, dried over Na2SC>4, and concentrated in vacuo. The crude product was purified by column chromatography using (1:9 EtOAc: Pet ether) over 230-400 flash silica to afford (8) in the form of two diastereomeric pairs (dr 8a:8b 3:1) as a colorless oil with an overall yield of 89% (260 mg).

[0112] Diastereomer A (8a): Colorless oil, 67 % (195 mg) isolated yield, Rf = 0.48 in 10% EtOAc:Pet ether. 'H NMR (400 MHz, CDCI3) 8 ppm 7.57 (d, J = 8.0 Hz, 2 H), 7.61 (d, J = 8.1 Hz, 2 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.39 - 7.33 (m, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 4.16 (q, J = 7.1 Hz, 2 H), 3.64 (m, 1 H), 2.89 (d, J = 6.8 Hz, 2 H), 2.80 - 2.68 (m, 1 H), 1.97 (m, 1 H), 1.53 (m, 1 H), 1.27 (t, J = 7.1 Hz, 3 H), 1.21 (d, J = 7.0 Hz, 3 H).13C NMR (101 MHz, CDCI3): <5 ppm 175.9, 140.8, 139.8, 136.4, 129.7, 128.8, 127.3, 127.2, 127.0, 62.4, 60.5, 41.1, 38.4, 36.6, 18.1, 14.2. HRMS (ESI) m / z calcd for C2oH2302N3Na [M+Na]+: 360.1682, found: 360.1676. Diastereomer B (8b): Colorless oil, 22 % (65 mg) isolated yield, Rf = 0.45 in 10% EtOAc: Pet Ether. 'H NMR (400 MHz, CDCI3) 8 ppm 7.60 (d, J = 8.3 Hz, 2 H), 7.57 (d, J = 8.0 Hz, 2 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.39 - 7.32 (m, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 4.17 (q, J = 7.1 Hz, 2 H), 3.66 - 3.53 (m, 1 H), 2.91 (d, J = 6.8 Hz, 2 H), 2.64 (q, J = 7.0 Hz, 1 H), 1.98 (m, 1 H), 1.63 (m, 1 H), 1.28 (t, J = 6.8 Hz, 3 H), 1.20 (d, 7= 7.0 Hz, 3 H).13C NMR (101 MHz, CDCI3): <5 ppm 176.1, 140.8, 139.8, 136.4, 129.7, 128.8, 127.4, 127.3, 127.0, 62.0, 60.6, 40.7, 37.7, 37.0, 17.0, 14.2. HRMS (ESI) m / z Calcd for C2oH2302N3Na [M+Na]+: 360.1682, found: 360.1678. d) Synthesis of Sacubitril (11)

[0113] The given Compound 11 prepared according to the same procedure as reported in the literature e.g. Kaur, A.; Gehlawat, A.; Prakash, R.; Pandey, S. K. Enantioselective Total Synthesis of Sacubitril. Chemistry Select, 2021, 6(33), 8928-8930. Obtained compound Orange gum, 74 % isolated yield.

[0114] Rf = 0.51 in 10% MeOH: DCM. ’H NMR (400 MHz, CDC13): 5 ppm 7.56 (d, J = 7.8 Hz, 2 H), 7.51 (d, J = 7.8 Hz, 2 H), 7.41 (t, J = 7.5 Hz, 2 H), 7.34 - 7.29 (m, 1 H), 7.23 (d, J = 7.8 Hz, 2 H), 6.02 (d, J = 8.5 Hz, 1 H), 4.34 - 4.15 (m, 1 H), 4.10 (q, J = 7.1 Hz, 2 H), 2.82 (m, 2 H), 2.62 (m, 2 H), 2.55 (m., 1 H), 2.49 - 2.33 (m, 2 H), 1.99 - 1.86 (m, 1 H), 1.57 - 1.45 (m, 1 H), 1.22 (t, J = 7.1 Hz, 3 H), 1.14 (d, J = 7.0 Hz, 3 H). 13C NMR (101 MHz, CDC13): 5 ppm 176.6, 172.0, 140.9, 139.5, 136.7, 130.0, 128.9, 127.3, 127.2, 127.1, 60.8, 48.9, 40.6, 37.4, 36.6, 31.0, 29.8, 17.8, 14.3. HRMS (ESI) m / z calcd for C24H30O5N [M+H]+: 412.2118, found: 412.2116. e) Synthesis of ethyl-5-([l,l'-biphenyl]-4-yl)-4-hydroxy-2-methylenepentanoate (7)

[0115] Compound 3af (100 mg) was dissolved in MeOH (3 mL) and cooled to -40 °C, to this cooled reaction mixture NaBHi (1.2 equiv.) was added and stirred at the same temperature for 2 h. After complete consumption of the starting material by TLC, the reaction was quenched by 1 mL AcOH. Volatiles were removed on vacuo and residue was dissolved in DCM followed by washing with brine. Further, the residue was purified by column chromatography using (1:9) EtOAc: Pet ether) over 230-400 flash silica gel to afford the ethyl-5-([l,l'-biphenyl]-4-yl)-4- hydroxy-2-methylenepentanoate (7) as a colorless oil with 98% yield.

[0116] Rf = 0.36 in 20% EtOAc:Pet ether. 'H NMR (400 MHz, CDCh): 8 ppm 7.60 (d, J = 8.1 Hz, 2 H), 7.56 (d, J = 7.9 Hz, 2 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.37 - 7.31 (m, 3 H), 6.29 (s, 1 H), 5.70 (s, 1 H), 4.24 (q, J = 7.0 Hz, 2 H), 4.12 - 4.05 (m, 1 H), 2.92 - 2.79 (m, 2 H), 2.68 (dd, J = 3.3, 14.0 Hz, 1 H), 2.45 (dd, J = 8.5, 14.0 Hz, 1 H), 1.32 (t, J = 7.1 Hz, 3 H).13C NMR (101 MHz, CDCh): 6 ppm 167.7, 141.0, 139.4, 137.6, 137.5, 129.9, 128.8, 127.8, 127.2, 127.2, 127.0, 71.5, 61.0, 43.3, 39.8, 14.2. HRMS (ESI) m / z calcd for C20H23O3 [M+H]+: 311.1642, found: 311.1637. f) Synthesis of ethyl-5-([l,l'-biphenyl]-4-yl)-4-azido-2-methylenepentanoate (9)

[0117] Compound 9 was prepared by following the same procedure used for compound 8, as described in (c). Colorless oil, 73 % isolated yield.

[0118] Rf= 0.51 in 10% EtOAc:Pet ether. 'H NMR (400 MHz, CDCh) 8 ppm 7.62 - 7.58 (m, 2 H), 7.57 (d, J = 8.3 Hz, 2 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.36 (d, J = 7.4 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 2 H), 6.37 - 6.30 (s, 1 H), 5.78 - 5.71 (s, 1 H), 4.27 - 4.20 (m, 2 H), 3.91 - 3.81 (m, 1 H), 2.95 - 2.85 (m, 2 H), 2.69 (dd, 7 = 4.3, 13.9 Hz, 1 H), 2.49 (dd, 7 = 9.1, 14.1 Hz, 1 H), 1.31 (t, 7 = 7.1 Hz, 3 H).13C NMR (101 MHz, CDCh): 8 ppm 166.6, 140.8, 139.8, 136.7, 136.5, 129.7, 128.8, 128.4, 127.3, 127.2, 127.0, 62.5, 61.0, 40.5, 37.4, 14.2. g) Synthesis of 4-((l -([1,1 '-biphenyl] -4-yl)-4-(ethoxycarbonyl)pent-4-en-2-yl)amino)-4- oxobutanoic acid (10)

[0119] Compound 10 was prepared by following the same procedure used for compound 11, as described in (d). White solid, m.p.: 105-107 °C, 78 % isolated yield.

[0120] Rf= 0.45 in 10% MeOH:DCM. 'H NMR (400 MHz, CDC13) 8 ppm 7.57 (d, J = 7.9 Hz, 2 H), 7.52 (d, J = 7.9 Hz, 2 H), 7.42 (t, J = 7.5 Hz, 2 H), 7.35 - 7.30 (m, 1 H), 7.26 (d, J = 7.8 Hz, 2 H), 6.24 (s, 1 H), 6.22 (s, 1 H), 5.60 (s, 1H), 4.32 (br. s., 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.95 (dd, J = 5.8, 13.6 Hz, 1 H), 2.79 (dd, J = 7.3, 13.6 Hz, 1 H), 2.61 (m, 2 H), 2.55 (m, 1H), 2.49 - 2.34 (m, 3 H), 1.31 - 1.27 (m, 3 H).13C NMR (101 MHz, CDCI3): 8 ppm 175.3, 171.1, 166.9, 139.9, 138.6, 136.3, 135.9, 128.9, 127.9, 127.0, 126.3, 126.3, 126.1, 60.3, 50.1, 39.6, 34.9, 29.9, 28.8, 13.2. HRMS (ESI) m / z calcd for C24H28O5N [M+H]+: 410.1962, found: 410.1959. h) Synthesis of Sacubitril (11) from (10)

[0121] To a solution of 10 (50 mg, 0.12 mmol, lequiv.) in MeOH (1 mL), catalytic Pd / Carbon was added and the resulting mixture was stirred under H2 atmosphere for 2 h. After complete consumption of the starting material, the reaction mixture was filtered through a pad of celite and concentrated under reduced pressure. Further, the residue was purified by column chromatography using (1:19 MeOH:DCM) over 230-400 flash silica gel to afford sacubitril (11) as an orange gum with 96% yield (48.5 mg). i) Synthesis of Sacubitril (11) from (9)

[0122] To a solution of compound 9 (100 mg, 0.30 mmol, 1 equiv.) in MeOH (2 mL) catalytic Pd / Carbon was added and the resulting mixture was stirred under H2 atmosphere for 2 h. After complete consumption of the starting material by TLC, the reaction mixture was filtered through a pad of celite and concentrated under reduced pressure. The reduced derivative thus obtained was used in the next step without purification. Further conversion of crude intermediate to 11 was done by reported procedure in the literature e.g. Liu, K. K.-C.; Sakya, S. M.; O’Donnell, C. J.; Flick, A. C.; Li, J. Synthetic Approaches to the 2009 New Drugs. Bioorg. Med. Chem. 2011, 19, 1136-1154.

[0123] Example 4: Preparation of gamma butyrolactone based compounds useful in alkaloids and API preparation using compound of formula 1, 1 or II

[0124] 1. Reduction of Ketone of Dienyl Ketone: Synthesis of Dimethyl (E)-2-(2 chlorophenyl)-2- hydroxyethylidene)-5-methylene hexanedioate (12)

[0125] Sodium borohydride (6.2 mg, 0.16 mmol, 1.1 equiv.) was added portion-wise to the solution of compound (5a) (50 mg, 0.15 mmol, 1 equiv.) in methanol (1 mL) at 0 °C. The mixture was stirred for an additional one hour at room temperature and the reaction progress was monitored by TLC. Upon completion, the reaction mixture was quenched with saturated NH4CI solution, extracted with ethyl acetate, washed with water and brine, dried over anhydrous Na2SC>4, and concentrated under reduced pressure. The residue was purified by column chromatography using (2:8 EtOAc:Pet ether) over 230-400 flash silica gel to furnish dimethyl (E)-2-(2 chlorophenyl)-2- hydroxyethylidene)-5 -methylene hexanedioate (12) as a colorless oil with 82% isolated yield.

[0126] Rf= 0.38 in 20% EtOAc:Pet ether. 'H NMR (400 MHz CDCI3): 8 ppm 7.37 - 7.31 (m, 4 H), 6.83 (d, J = 9.0 Hz, 1 H), 6.16 (s, 1 H), 5.59 (s, 1 H), 5.51 (d, J = 9.0 Hz, 1 H), 3.77 - 3.67 (m, 6 H), 2.66 - 2.57 (m, 2 H), 2.48 - 2.43 (m, 2 H).13C NMR (101 MHz, CDCI3): 8 ppm 167.8, 167.6, 142.5, 140.4, 139.5, 133.8, 132.0, 128.8, 127.6, 126.3, 69.4, 52.0, 52.0, 31.8, 26.8. HRMS (ESI) m / z calcd for Ci?Hi9O535ClNa[M + Na]+: 361.0813, found: 361.0808.

[0127] 2. Reduction of Double Bonds of Dienyl Ketone: Dimethyl 2-(2-(4-chlorophenyl)-2- oxoethyl)-5-methylhexanedioate (13)

[0128] To the solution of compound (5a) (100 mg, 0.30 mmol, lequiv.) in MeOH (2 mL) catalytic Pd / Carbon was added and the resulting mixture was stirred under H2 atmosphere for 2 h. After complete consumption of the starting material by TLC, the reaction mixture was filtered through a pad of celite and concentrated under reduced pressure. The residue was purified by column chromatography using (1:9 EtOAc:Pet ether) over 230-400 flash silica gel to afford dimethyl 2- (2-(4-chlorophenyl)-2- oxoethyl)-5 -methylhexanedioate (13) as a colorless oil with 85% yield isolated yield, Rf= 0.48 in 20% EtOAc:Pet ether.

[0129] 'H NMR (400 MHz CDCI3): 8 ppm = 7.90 (d, J = 8.5 Hz, 2 H), 7.44 (d, J = 8.5 Hz, 2 H), 3.70 (s, 3 H), 3.67 (d, J = 2.4 Hz, 3 H), 3.50 - 3.37 (m, 1 H), 3.12 - 2.96 (m, 2 H), 2.46 (td, J = 6.7, 13.4 Hz, 1 H), 1.79 - 1.68 (m, 2 H), 1.66 (d, J = 5.8 Hz, 1 H), 1.54 - 1.42 (m, 1 H), 1.17 (d, J = 7.0 Hz, 3 H).13C NMR (101 MHz, CDCh): 8 ppm 196.6, 176.5, 176.4, 175.4, 175.3, 139.5, 134.6, 129.2, 128.7, 51.7, 51.4, 40.0, 39.9, 39.7, 39.1, 38.9, 30.9, 30.7, 29.5, 29.3, 16.9. HRMS (ESI) m / z calcd for Ci7H22O535Cl [M+H]+: 341.1150, found: 341.1146.

[0130] 3. Synthesis of / -butyrolactone from dienyl ketone: Methyl 4-(5-(4-chlorophenyl)-2- oxotetrahydrofuran-3-yl)-2-methylbutanoate (14)

[0131] Sodium borohydride (6.1mg, 0.16 mmol, 1.1 equiv.) was added portion-wise to the solution of compound (13) (0.15 mmol, 1 equiv.) in methanol (1 mL) at 0 °C. The mixture was stirred for an additional one hour at room temperature and the reaction progress was monitored by TLC. The reaction mixture was quenched with saturated NH4CI solution, extracted with ethyl acetate, washed with water and brine, dried over anhydrous Na2SC>4, and concentrated under reduced pressure. The residue was purified by column chromatography using (1:9 EtOAc:Pet Ether) over 230-400 flash silica gel to furnish the mixture of corresponding diastereomers of lactone (14) as a colorless oil with 84% yield (38.3 mg).

[0132] Isomer-A: Colorless oil, 23 % (10.02 mg) isolated yield, Rf = 0.33 in 20% EtOAc: Pet Ether. 'H NMR (400 MHz CDCh): 8 ppm 7.40 - 7.34 (m, 2 H), 7.29 (s, 2 H), 5.39 - 5.29 (m, 1 H), 3.67 (d, J = 3.3 Hz, 3 H), 2.83 - 2.69 (m, 2 H), 2.53 - 2.41 (m, 1 H), 2.03 - 1.86 (m, 1 H), 1.86 - 1.72 (m, 2 H), 1.72 - 1.60 (m, 1 H), 1.60 - 1.36 (m, 2 H), 1.18 (dd, J = 4.4, 7.1 Hz, 3 H).13C NMR (101 MHz, CDCh): P ppm 177.9, 177.8, 176.6, 137.6, 137.5, 137.0, 134.4, 129.0, 129.0, 126.8, 126.8, 78.7, 78.6, 78.6, 51.9, 51.7, 51.7, 41.4, 41.2, 40.8, 39.3, 39.2, 37.9, 37.7, 37.5, 31.5, 31.0, 29.0, 28.1, 27.7, 17.2, 17.0, 12.7. HRMS (ESI) m / z calcd for Ci6H20O435Cl [M+H]+: 311.1045, found: 311.1038.

[0133] Isomer-B: Colorless oil, 61% (27.8 mg) isolated yield, Rf =0.29 in 20% EtOAc:Pet ether. 'H NMR (400 MHz CDCh): 8 ppm 7.37 (d, J = 8.4 Hz, 2 H), 7.24 (d, J = 8.4 Hz, 2 H), 5.60 - 5.48 (m, 1 H), 3.68 (d, J = 4.6 Hz, 3 H), 2.61 (dd, J = 8.8, 14.1 Hz, 1 H), 2.52 - 2.45 (m, 1 H), 2.45 - 2.34 (m, 2 H), 1.94 - 1.87 (m, 1 H), 1.84 - 1.70 (m, 1 H), 1.61 - 1.46 (m, 2 H), 1.19 (d, J = 7.0 Hz, 3 H).13C NMR (101 MHz, CDCh): 8 ppm 178.3, 178.2, 176.4, 176.4, 138.0, 137.8, 136.8, 136.5, 134.0, 133.9, 130.4, 128.8, 128.8, 128.5, 128.0, 126.1, 126.1, 124.7, 77.7, 77.7, 77.6, 51.7, 51.5, 39.1, 38.9, 38.6, 38.3, 37.8, 36.2, 36.0, 35.5, 31.3, 30.8, 29.5, 28.8, 28.1, 27.7, 22.5, 17.1, 16.8, 12.5. HRMS (ESI) m / z calcd for Ci6H2o0435Cl [M+H]+: 311.1045, found: 311.1039.

[0134] ADVANTAGES OF THE INVENTION

[0135] 1. The use of MBH adducts as reagents (electrophiles) allows for a streamlined and straightforward synthesis process, resulting in high yields of the desired compounds.

[0136] 2. The process utilizes a metal-free catalytic approach, eliminating the need for expensive or toxic metal catalysts, reducing not only the cost of the synthesis process but also offers a more sustainable and environmentally friendly approach.

[0137] 3. The process provides high selectivity for the synthesis of the desired compounds.

[0138] 4. The invention enable the synthesis of Sacubitril API and related compounds using the novel compounds of formula I as starting materials or intermediates.

[0139] 5. Present invention provide alternative transition metal free path for Tsuji Trost type allylation reactions.

Claims

We Claim:

1. A compound of formula 1Formula 1 wherein, n is 1 or 2;A isR, Ri and Ri ’ are same or different, and are independently selected from the group consisting of hydrogen, (un)substituted alkyl (Cl to C21), (un)substituted alkoxy (Cl to C21), (un)substituted aryl (C5-C11), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un) substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether-(un)substitutedaryl, (un)substitutedalkyl-ether-(un)substitutedheteroaryl, (un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl-thio-(un)substitutedaryl, (un)substitutedalkyl- thio-(un)substitutedheteroaryl, (un)substitutedalkyl-thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate.

2. The compound as claimed in claim 1 , wherein the compound of formula 1 is selected from compound of formula I and formula IIFormula I Formula II wherein R, R1 and R1 ’ are same as defined in claim 1.

3. The compound as claimed in claim 2, wherein the said compound of formula II is selected from a group consisting of: i. Dimethyl (E)-2-(2-(4-chlorophenyl)-2-oxoethylidene)-5-methylenehexanedioate (Ha), ii. Dimethyl (E)-2-(2-(4-bromophenyl)-2-oxoethylidene)-5-methylenehexanedioate(Hb), iii. Dimethyl (E)-2-(2-(4-cynophenyl)-2-oxoethylidene)-5-methylenehexanedioate (He), iv. Dimethyl (E)-2-(2-methylene-5-(2-oxo-2-phenylethylidene)hexanedioate (lid), v. Dimethyl (E)-2-(2-(4-iodophenyl)-2-oxoethylidene)-5-methylenehexanedioate (He), vi. Dimethyl (E)-2-(2-(4-(methoxycarbonyl)phenyl)-2-oxoethylidene)-5- methylenehexanedioate (Ilf), vii. Dimethyl (E)-2-(2-(4-flurophenyl)-2-oxoethylidene)-5-methylenehexanedioate (Hg), viii. Dimethyl (E)-2-methylene-5-(2-oxo-2-p-tolyl)ethylidene) hexanedioate (Hh), ix. dimethyl (E)-2-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-methylenehexanedioate (Hi), x. Dimethyl (E)-2-(2-(4-hydroxyphenyl)-2-oxoethyli dene)-5 -methylenehexanedioate (Hj), xi. Dimethyl (E)-2-(2-(3-chlorophenyl)-2-oxoethylidene)-5-methylenehexanedioate(Hk), xii. Dimethyl (E)-2-(2-(3-bromophenyl)-2-oxoethylidene)-5-methylenehexanedioate(HI)xiii. Dimethyl (E)-2-(2-(3-methoxyphenyl)-2-oxoethylidene)-5-methylenehexanedioate (Um), xiv. Dimethyl(E)-2-methylene-5-(2-oxo-2- (3(trifluoromethoxy)phenyl)ethylidene)hexanedioate(IIn), xv. Dimethyl(E)-2-methylene-5-(2-oxo-2-(3 -(trifluoromethyl )phenyl)ethylidene) hexanedioate (Ho), xvi. Dimethyl (E)-s2-methylene-5-(2-oxo-2-(m-tolyl)ethylidene) hexanedioate (Up), xvii. Dimethyl (E)-2-methylene-5-(2-(3-nitrophenyl)-2-oxoethylidene)hexanedioate (Ilq), xviii. Dimethyl (E)-2-(2-(2-fluorophenyl)-2-oxoethylidene)-5-methylenehexanedioate(Hr), xix. Dimethyl (E)-2-methylene-5-(2-oxo-2-(l-(phenylsulfonyl)-lH-indol-3- yl)ethylidene)hexanedioate (Ils), xx. Dimethyl (E)-2-methylene-5-(2-oxo-2-(quinolin-2-yl) ethylidene)hexanedioate (lit), xxi. Dimethyl (E)-2-methylene-5-(2-(naphthalen-2-yl)-2-oxo ethylidene)hexanedioate(Hu), xxii. Dimethyl (E)-2-(2-(3,4-difluorophenyl)-2-oxoethylidene)-5-methylenehexanedioate(Hv), xxiii. Dimethyl (E)-2-methylene-5-(2-oxoheptylidene) hexane -dioate (IIw), xxiv. Dimethyl (E)-2-methylene-5-(2-oxo-2-(lH-pyrrol-2-yl) ethylidene)hexanedioate (IIx), xxv. Dimethyl (E)-2-methylene-5-(2-oxo-2-(thiophen-2-yl) ethylidene)hexanedioate (Uy), xxvi. Dimethyl (E)-2-methylene-5-(2-oxo-2-(pyridin-2-yl)ethyli -dene)hexanedioate (Hz), xxvii. Tetramethyl 5,5'-(l,3-phenylenebis(2-oxoethan-2-yl-l-ylidene))(5E,5'E)-bis(2- methylene hexanedioate) (Ilaa), xxviii. Dimethyl (E)-2-(2-cyclopentyl-2-oxoethylidene)-5-methylenehexanedioate (Ilab), xxix. Dimethyl (E)-2-(3-methyl-2-oxobutylidene)-5-methyl-lene hexanedioate (Ilac), xxx. Diethyl (E)-2-(2-(4-chlorophenyl)-2-oxoethylidene)-5-methylenehexanedioate(Had), xxxi. Dimethyl 3-(4-chlorobenzoyl)-2,5-dimethylene hexanedioate (Ilae),xxxii. 6-Ethyl 1 -methyl (E)-2-(2-(4-chlorophenyl)-2-oxoethyl -idene)-5- methylenehexanedioate (Ilf), and xxxiii. Dimethyl (E)-3-(4-chlorophenyl)-5-(2-(4-chlorophenyl)- 2-oxoethylidene)-2- methylenehexanedioate (Hag).

4. The compound as claimed in claim 1, wherein the said compound of formula I is selected from a group consisting of: i. Methyl 4-(4-chlorophenyl)-2-methylene-4 oxobutanoate (la), ii. Methyl 4-(4-fluorophenyl)-2-methylene-4-oxobutanoate (Id), iii. Methyl 4-(4-iodophenyl)-2-methylene-4-oxobutanoate (le), iv. Methyl 4-(4-bromophenyl)-2-methylene-4-oxobutanoate (If), v. Methyl 2-methylene-4-oxo-4-(p-tolyl)butanoate (Ig), vi. Methyl 4-(4-ethylphenyl)-2-methylene-4-oxobutanoate (Ih), vii. Methyl 4-(4-isopropylphenyl)-2-methylene-4-oxobutanoate (Ii), viii. Methyl 2-methylene-4-(4-nitrophenyl)-4-oxobutanoate (Ij), ix. Methyl 4-(4-methoxyphenyl)-2-methylene-4-oxobutanoate (Ik), x. Methyl 4-(4-hydroxyphenyl)-2-methylene-4-oxobutanoate (II), xi. Methyl 4-(3-chlorophenyl)-2-methylene-4-oxobutanoate (Im), xii. Methyl 4-(3-bromophenyl)-2-methylene-4-oxobutanoate (In), xiii. Methyl 4-(3-methoxyphenyl)-2-methylene-4-oxobutanoate (Io), xiv. Methyl 2-methylene-4-oxo-4-(3-(trifluoromethoxy)phenyl) butanoate (Ip), xv. Methyl 2-methylene-4-oxo-4-(3-(trifluoromethyl)phenyl) butanoate (Iq), xvi. Methyl 2-methylene-4-oxo-4-(m-tolyl)butanoate (Ir), xvii. Methyl 4-(furan-2-yl)-2-methylene-4-oxobutanoate (Is), xviii. Methyl 2-methylene-4-oxo-4-(thiophen-2-yl)butanoate (It), xix. Methyl 2-methylene-4-oxo-4-(lH-pyrrol-2-yl)butanoate (lu), xx. Methyl 2-methylene-4-oxo-4-(l-(phenylsulfonyl)-lH-pyrrol-2-yl)butanoate (Iv), xxi. Methyl 2-methylene-4-oxo-4-(pyridin-2-yl)butanoate (Iw), xxii. Methyl 2-methylene-4-oxo-4-(quinolin-2-yl)butanoate (ly), xxiii. Methyl 2-methylene-4-oxo-4-(pyridin-3-yl)butanoate (Iz), xxiv. Methyl 4-(2-fluorophenyl)-2-methylene-4-oxobutanoate (laa), xxv. Methyl 4-(lH-indol-3-yl)-2-methylene-4-oxobutanoate (lab),xxvi. Methyl 2-methylene-4-oxo-4-(l-(phenylsulfonyl)-lH-indol-3-yl)butanoate (lac), xxvii. Methyl 4-(benzo[d][l,3]dioxol-5-yl)-2-methylene-4-oxo butanoate (lad), xxviii. Methyl 4-(5-bromo-lH-indol-3-yl)-2-methylene-4-oxo butanoate (lae), xxix. Methyl 4-(ferrocene)-2-methylene-4-oxobutanoate (laf), xxx. Dimethyl 4,4'-(l,3-phenylene)bis(2-methylene-4-oxobutanoate) (lag), xxxi. Methyl 2-methylene-4-oxo-5-phenylpentanoate (lah), xxxii. Methyl 4-(3,4-difluorophenyl)-2-methylene-4-oxo butanoate (lai), xxxiii. Methyl 5-([l,l'-biphenyl]-4-yl)-2-methylene-4-oxo butanoate (laj), xxxiv. Methyl 2-methylene-4-oxononanoate (lak), xxxv. Methyl 2-methylene-4-oxopentanoate (lam), and xxxvi. Methyl 4-cyclopentyl-2-methylene-4-oxobutanoate (Ian).

5. A process for the preparation of compounds of formula 1 as claimed in claim 1, wherein the said process comprising the steps of: c) carrying out reaction of substituted aldehyde of formula A with substituted Morita- Baylis-Hillman adducts of formula B in presence of N-Heterocyclic carbene (NHCs) as formula C as catalyst, organic or inorganic base and solvent at a temperature in the range of 30-70 °C for a time period in the range of 0.5 to 20 hr to obtain the said compound of formula I of Formula 1 and crude of formula II of Formula 1 respectively; wherein R, Ri and Rf are same as defined in claim 1 or 2;R2, R3 and R4 are independently selected from the group consisting of C1-C6 (un)substituted alkyl, C1-C6 (un)substituted cycloalkyl, and (un)substituted aryl; and d) treating the crude of formula II of Formula 1 obtained in step a) with solvent at a temperature in the range of 65-75°C and for a time period in the range of 6-7 h to obtain compound of formula II of Formula 1.

6. The process as claimed in claim 5, wherein N-heterocyclic carbenes (NHCs) catalyst is selected from the group consisting of7. The process as claimed in claim 5, wherein the solvent used is selected from a group consisting of dichloromethane (DCM), acetonitrile (ACN), dimethylformamide (DMF), toluene, 1,4-dioxane, 1,2-dichloroethane (DCE), dimethyl sulfoxide (DMSO), Heptane, o- xylene, Chlorobenzene, Cyclohexane, Diethyl ether, Isopropyl alcohol, Chloroform, tetrahydrofuran, hexafluro-2-propanol, o-dichlorobenzene, isoamyl alcohol, n-propyl alcohol, Acetone, Ethyl Acetate, Dimethyl acetamide, ethyl methyl ketone, MTBE, methanol, N-methyl morpholine, N- methyl pyrrolidone, water, carbon tetrachloride, 1,1, 2, 2 tetrachloroethane or mixture thereof.

8. The process as claimed in claim 5, wherein the inorganic base used for the preparation of compound of formula I, and the organic base is used for the preparation of compound of formula II; wherein the inorganic base is selected from cesium carbonate, sodium carbonate, potassium carbonate, sodium butoxide, sodium hydride, and 4-dimethylaminopyridine; and wherein the organic base is selected from l,4-diazabicyclo[2.

2. 2]octane (DABCO), 4- dimethylaminopyridine, 1,8-Diazabicyclo 5.4.0 undec-7-ene (DBU), dimethylacetamide (DMA), and pyridine.

9. A process of preparation of sacubitril using said compound of formula 1, I or II as claimed in claim 1 or 2, wherein said process comprises steps of: a) mixing and reacting the compound of formula 1, I or II being an intermediate compound in methanol in presence of catalyst Pd / Carbon under stirring and hydrogen gas at temperature in the range of 25-35 °C for time period in the range of 1.5-2.5 h to obtain a crude mixture; b) dissolving the crude mixture as obtained in step a) directly without purifying in methanol, cooling to temperature of -40 °C followed by reacting with sodium borohydride as reducing agent for time period in the range of 1.5-3.5 h to obtain intermediate compound 6;c) dissolving the intermediate compound 6 as obtained in step b) in dichloromethane followed by reacting with dropwise addition of methane sulfonyl chloride in presence of triethylamine as base and 4-(dimethylamino)pyridine as catalyst under stirring at temperature in the range of 0-2 °C for time period in the range of 1.5-2.5 h to obtain crude mesylate mixture; d) reacting the said crude mesylate mixture as obtained in step c) with sodium azide in presence of dimethyl formamide as solvent at temperature in the range of 50-70 °C for time period in the range of 5-7 h to obtain intermediate compound 8 in the form of diastereomers 8a and 8b; e) mixing and reacting the intermediate compound 8a as obtained in step d) with triphenylphosphine in presence of chloroform as solvent under stirring at temperature in the range of 25-35 °C to obtain a solution mixture; f) adding triethyl amine and succinic anhydride sequentially in the solution mixture as obtained in step e) and reacting under reflux for time period in the range of 3-5 h to obtain the sacubitril.

10. A process of preparation of sacubitril using said compound of formula 1, I or II as claimed in claim 1 or 2, wherein said process comprises steps of: a) mixing and reacting the compound of formula 1, I or II being an intermediate compound in methanol and cooled down to temperature of -40 °C followed by reacting with sodium borohydride as reducing agent for time period in the range of 3-5 h to obtain intermediate compound 7 ; b) reacting the said intermediate compound 7 as obtained in step b) with sodium azide in presence of dimethyl formamide as solvent at temperature in the range of 50-70 °C for time period in the range of 5-7 h to obtain intermediate compound 9; c) mixing and reacting the intermediate compound 9 as obtained in step b) with triphenylphosphine in presence of chloroform as solvent under stirring at temperature in the range of 25-35 °C to obtain a solution mixture; d) adding triethyl amine and succinic anhydride sequentially in the solution mixture as obtained in step c) and reacting under reflux for time period in the range of 3-5 h to obtain intermediate compound 10;e) mixing and reacting the intermediate compound 10 as obtained in step (d) in methanol in presence of catalyst Pd / Carbon under stirring and hydrogen gas at temperature in the range of 25-35 °C for time period in the range of 1.5-2.5 h to obtain sacubitril.

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