TECHNOLOGY FOCUS - ORGANIC CHEMISTRY - Preparation (claimed): The synthesis of (o) comprises: conversion of (v) to 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(dimethyl carbamoyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid methyl ester (x) by selective hydrogenation of benzyloxy carbonyl group in (v) to give intermediate methyl (2S)-8-azabicyclo(3.2.1)oct-3-yl((2-hydroxy-1-(1R)-phenylethyl)amino)-exo-acetate hydrochloride salt (ix) using Pd/C catalyst at an elevated pressure of hydrogen at room temperature followed by regio-selective introduction of N,N-dimethylcarbamoyl group on the bridge head nitrogen in the presence of an organic base such as diisopropylethylamine or triethylamine or using an inorganic bases such as cesium carbonate in an appropriate organic solvents such as dimethyl formamide or dimethyl acetamide or in any water miscible cyclic ether; or conversion of (iv) to (x) by treating a solution of (iv) with dry hydrogen chloride gas for extended period of time at room temperature to give (ix) followed by regio-selective introduction of N,N-dimethyl carbamoyl group using N,N-dimethyl carbamoyl chloride or N,N-dimethylamine and triphosgene on the bridge head nitrogen in the presence of an organic base such as diisopropylethylamine or triethylamine or using an inorganic bases such as cesium carbonate in an appropriate organic solvents such as dimethyl formamide or dimethyl acetamide or in any water miscible cyclic ether at 0-35 degrees C; and conversion of (x) to (o) in two steps comprising of removal of the phenyl ethanol group in (x) by hydrogenation in presence of Pd/C catalyst and acetic acid in an organic solvent such as methanol at around 20 Kg hydrogen pressure to form (S)-amino-(8-dimethylcarbamoyl-8-aza-bicyclo(3.2.1)oct-3-yl)-acetic acid methyl ester (xi), followed by protection of the free amine by treatment with di-tert-butyl dicarbonate in dichloromethane, where such that at each step the intermediates were optionally isolated and purified with suitable process.The synthesis of methyl (2S)-2-(tert-butoxycarbonyl)-amino-2-(-8-azabicyclo(3.2.1)oct-3-yl)-exoacetate comprises hydrogenolysis of methyl (2S)-2-((tert-butoxycarbonyl)-(benzyloxy carbonyl)-amino)-2-(8-(benzyloxy carbonyl)-8-azabicyclo(3.2.1)oct-3-yl)-exo-acetate in presence of palladium supported on charcoal at around 5 Kg pressure of hydrogen at room temperature followed by isolation of the product.The synthesis of methyl (2S)-2-(tert-butoxycarbonyl)-amino-2-(-8-(dimethylcarbamoyl)-8-azabicyclo(3.2.1)-oct-3-yl)-exo-acetate comprises hydrogenolysis of 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(dimethyl carbamoyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid methyl ester in presence of palladium supported on charcoal at around 5 Kg pressure of hydrogen at room temperature followed by treatment with di-tert-butyl dicarbonate in dichloromethane at 0-35 degrees C.The synthesis of methyl (2S)-2-(tert-butoxycarbonyl)-amino-2-(-8-azabicyclo(3.2.1)oct-3-yl)-exo-acetate comprises conversion of (xv) to methyl (2S)-2-((tert-butoxycarbonyl)-amino)-2-(8-(benzyloxy carbonyl)-8-azabicyclo(3.2.1)oct-3-yl)-exo-acetate (m) first by treatment with methanolic-hydrochloride, followed by treatment with di-tert-butyl dicarbonate, further hydrogenolysis of (m) over palladium supported on charcoal (Pd/C) to give the product.The methyl (2S)-2-((tert-butoxycarbonyl)-(benzyloxy carbonyl)-amino)-2-(8-(benzyloxy carbonyl)-8-azabicyclo (3.2.1)oct-3-yl)-exo-acetate is synthesized by reaction of methyl (2S)-2-(benzyloxycarbonyl)-amino-2-(-8-(benzyloxy carbonyl)-8-azabicyclo(3.2.1)oct-3-yl)-exo-acetate with di-tert-butyl dicarbonate and 4-dimethylamino pyridine in an aprotic organic solvent such as acetonitrile at room temperature.The methyl (2S)-2-(benzyloxycarbonyl)-amino-2-(-8-(benzyloxy carbonyl)-8-azabicyclo-(3.2.1)oct-3-yl)-exo-acetate is prepared by reaction of methyl (2S)-2-amino-2-(8-azabicyclo-(3.2.1)oct-3-yl)-exo-acetate hydrochloride with benzyloxy carbonyl chloride in the presence of aqueous sodium bicarbonate solution in aqueous 1,4-dioxane at 0 degrees C.The methyl (2S)-2-amino-2-(8-azabicyclo-(3.2.1)oct-3-yl)-exo-acetate hydrochloride is prepared by hydrogenolysis of 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid methyl ester hydrochloride over palladium supported on charcoal at around 20 Kg pressure of hydrogen at 60 degrees C in an organic solvent such as methanolic hydrochloric acid.The 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1R)-carboxylic acid methyl ester hydrochloride is prepared by a process comprising hydrolysis of the nitrile group in 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carbonitrile using methanolic-hydrochloride at room temperature.The 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carbonitrile is prepared by a process comprising of reaction of benzyl 3-exoformyl-8-azabicyclo(3.2.1)octane-8-carboxylate with R-(-)-2-phenyl glycinol and trimethylsilylcyanide in an organic solvent comprising dichloromethane, methanol, chloroform, 1,2-ethylenedichloride, hexane, tetrahydrofuran, methyltetrahydrofuran and/or DME under standard Strecker reaction conditions in the presence of acetic acid, or Lewis acid at -40 and 25 degrees C.The benzyl 3-exo-formyl-8-azabicyclo(3.2.1)octane-8-carboxylate is prepared by a process comprising: (a) reaction of 8-methyl-8-azabicyclo(3.2.1)octan-3-one with benzyl chloroformate in presence of an inorganic base such as potassium carbonate in a organic solvent such as toluene at an ambient temperature to obtain benzyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylate followed by optional isolation and purification of the product; (b) reaction of benzyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylate with ylide obtained by reaction of sodium hydride and trimethylsulfonium iodide in an organic solvent such as dimethylformamide at room temperature to obtain benzyl 8H-spiro(8-azabicyclo(3.2.1)octane-3,2'-oxirane)-8-carboxylate followed by optional isolation and purification of the product; (c) reaction of benzyl 8H-spiro(8-azabicyclo(3.2.1)octane-3,2'-oxirane)-8-carboxylate with trifluoride-diethyl (BF3)-etherate in an organic solvent such as dichloromethane at room temperature to obtain benzyl 3-exo-formyl-8-azabicyclo(3.2.1)octane-8-carboxylate followed by optional isolation and purification of the product.The process further comprises conversion of (n) to compound of formula (o) comprising either a carbonyl insertion reaction between intermediate (o) and N,N-dimethyl amine using triphosgene or di-tert-butyl dicarbonate or 1,1-carbonyl bis-imidazole and an organic base such as diisopropyl ethylamine, triethylamine or an inorganic base such as cesium carbonate in an appropriate organic solvent such as dimethylformamide, dimethylacetamide or any water miscible cyclic ether; or treatment of (n) with N,N-dimethyl carbamoyl chloride in presence of a suitable base such as triethylamine, N,N-diisopropyl ethyl amine in an organic solvent. In the process, 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(dimethyl carbamoyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid methyl ester is synthesized by a process comprising selective hydrogenation of 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo methane-1-(1S)-carboxylic acid methyl ester hydrochloride salt using palladium supported on carbon at around 5 Kg pressure of hydrogen at room temperature followed by treatment with N,N-dimethylcarbamoyl chloride or dimethylamine and triphosgene in presence of a suitable base such as N,N-diisopropyl ethylamine or triethylamine, or using an inorganic base such as cesium carbonate in an appropriate organic solvents such as dimethyl formamide or dimethyl acetamide or in any water miscible cyclic ether at 0-35 degrees C. In the process, 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(dimethyl carbamoyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid methyl ester is synthesized by a process comprising selective hydrogenation of 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo methane-1-(1S)-carboxylic acid methyl ester hydrochloride salt using palladium supported on carbon at around 5 Kg pressure of hydrogen at room temperature followed by treatment with N,N-dimethylcarbamoyl chloride or dimethylamine and triphosgene in presence of a suitable base such as N,N-diisopropyl ethylamine or triethylamine, or using an inorganic base such as cesium carbonate in an appropriate organic solvents such as dimethyl formamide or dimethyl acetamide or in any water miscible cyclic ether at 0-35 degrees C. In the process, 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(75)-carboxylic acid methyl ester hydrochloride salt is synthesized by a process comprising selective hydrogenation of 1-(2-hydroxy-1-(1R)-phenylethyl amino)-1-(8-(benzyloxy carbonyl)-8-azabicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid methyl ester hydrochloride salt using palladium supported on carbon at around 5 Kg pressure of hydrogen at room temperature followed by treatment with dimethylamine and triphosgene in presence of a suitable base such as N,N-diisopropyl ethylamine or triethylamine, or using an inorganic base such as cesium carbonate in an appropriate organic solvents such as dimethyl formamide or dimethyl acetamide or in any water miscible cyclic ether at 0-35 degrees C. In the process, 1-(R or S-tert-butylsulfinylamino)-1-(8-(benzyloxy carbonyl)-8-aza-bicyclo(3.2.1)-oct-3-yl)-exo-methane-1-(1S)-carboxylic acid ethyl ester with methanolic-hydrochloride is prepared by conversion of benzyl exo-3-(ethoxy or methoxy (oxo)acetyl)-8-azabicyclo(3.2.1)octane-8-carboxylate (xiii) to (xv) by first treating (xiii) with either (R)-(+)-2-methyl-2-propane sulfinamide or with (S)-(-)-2-methyl-2-propane sulfinamide in the presence of titanium(IV) ethoxide and followed by further reduction of the intermediate ketimine (xiv) using a suitable reducing agent such as sodium borohydride or sodium triacetoxy borohydride or modified borohydrides derived from a combination of sodium borohydride with chiral acid such as camphoric acid or tartaric acid or with chiral acid such as succinic or phthalic acid. In the process, benzyl exo-3-(ethoxy or methoxy(oxo)acetyl)-8-azabicyclo(3.2.1)octane-8-carboxylate is prepared by a process comprising treatment of (xii) with methanolic-hydrochloride. In the process, benzyl 3-(1-formamido-2-ethoxy-2-(oxo)ethylidene)-8-azabicyclo(3.2.1)-octane-8-carboxylate is prepared by a process comprising condensation of (i) to with an active methylene compounds such as methyl or ethyl isocyanoacetate. ACTIVITY - Antidiabetic.    MECHANISM OF ACTION - Dipeptidyl peptidase-IV inhibitor.    EXAMPLE - A solution of methyl (2S)-2-((tert-butoxycarbonyl)-(benzyloxy carbonyl)-amino)-2-(8-(benzyloxy carbonyl)-8-azabicyclo(3.2.1)oct-3-yl)-exo-acetate (3.5 g) was hydrogenated over palladium supported on charcoal (0.35 g) using a positive pressure of hydrogen (5 Kg) at room temperature for 2 hours. The reaction mixture was filtered and the filtrate was concentrated to dryness to give methyl (2S)-2-(tert-butoxycarbonyl)-amino-2-(-8-azabicyclo(3.2.1)oct-3-yl)-exo-acetate (1.50 g, 89%).