3-(2-FLUORO-PHENYL)-3-OXO-PROPIONICACIDETHYLESTER

Experimental operation: Take malonate potassium salt 1.00 g (about 5.47mmol) of anhydrous magnesium chloride and 0.65 g (About 6.84mmol) in 25 mLround bottom flask was added dropwise 0.55 g of triethylamine was added after 6mL of acetonitrile was dissolved, stirred 30 min at room temperature. Thendropped by 2 mL of acetonitrile was dissolved 0.48 g (2.5 mmol) o-fluorobenzoyl chloride ld, supplemented triethylamine 0.06 mL, stirred atroom temperature overnight. After treatment: 30 mL of water was added to dilutethe reaction solution, and then were added 30, 20, 20 mL ethyl acetate, and theethyl acetate layer was collected. After 30 mL with saturated brine ethylacetate layer was dried over anhydrous sodium sulfate, and spin dry columnchromatography (PE: EA = 15: 1) to give the product isolated 2d, in 92percent yield.Example-12: Preparation of compound of Formula Xlla. 2-fluorobenzoic acid (lOg) toluene (80ml) and dimethyl formamide (0.1ml) were charged into a round bottom flask at 25-35°C. To the reaction mass thionyl chloride (12.7g) was added slowly over a period of 30min at same temperature. Reaction mass was heated to reflux and stirred for 3-4hr. After completion of the reaction, reaction mass was cooled to 55-65°C and distilled completely under vacuum at 55-65°C and co-distilled with toluene (2x20ml) to obtain residue and the residue was dissolved in tetrahydrofuran (50ml). Tetrahydrofuran (150ml) and magnesium chloride (24.5g) was added in another round bottom flask at 25-35°C. Reaction mass was cooled to 10-15°C and was added potassium salt of monoethylmalonate (36.4g) at same temperature. To the reaction mass was added triethyl amine (21.6g) slowly over a period of 30min and reaction mass was heated to 25- 35 °C and stirred for 8hr at same temperature. To the reaction mass was added above pre dissolved tetrahydrofuran solution of 2-fluorobenzoyl chloride at 15-25°C and stirred for 16hr at 25-35°C. After completion of the reaction, reaction mass was distilled completely under vacuum at below 50°C and cooled to 25-35°C. To the resultant reaction mass was added water (400ml) and stirred for 3hr at same temperature. Filtered the precipitated solids and washed with water (10ml). The obtained solids were stirred with water (200ml), and a mixture of water (100ml) and sodium bicarbonate (50g), a mixture of water (100ml) and hydrochloric acid (10ml) sequentially at 25-35°C and filtered the solid and washed with water (10ml). The obtained solid was stirred with methanol (20ml) for 40min at 25-35°C. Filtered the solids and washed with methanol (10ml) and dryed the material to obtain title compound. Yield: 13.5 g.Under nitrogen atmosphere, 30 ML of THF was added to 6.09 g (10 mmol, 1.0 equivalent) of (BrZnCH2COOEt*THF)2.. General procedure: The substrate b-ketoesters 10 a–n were either purchased or synthesized following published procedures. Some benzoylacetates were commercially available. Ethyl 3-oxo-3-phenyl propanoate (10a) was purchased. The reaction of benzoylacetates 10 b–n was prepared as described in previous reports. 25–27 A solution of a substituted acetophenone 8 a–n (0.05 mol) dissolved in toluene (50 mL) was added dropwise to a solution containing diethyl carbonate (9) (0.10 mol) and sodium hydride (0.15 mol 60percent dispersion in mineral oil). The mixture was stirred at room temperature, and then refluxed for 30 min. The mixture was poured into ice water, acidified with glacial acetic acid, and extracted with EtOAc (3x100 mL). The EtOAc extract was then dried over anhydrous MgSO4. After removal of the solvent in vacuo, the crude products were purified by silica gel column chromatography eluting with dichloromethane to afford benzoylacetates 10 b–n. All synthetic compounds were in agreement with 1H NMR, 13C NMR, IR and mass spectroscopic data.General procedure: A mixture of an appropriate dione (9a or 9b) (0.3 mol) and EtOH (500 mL) was heated to 80 °C refluxing for 5 h. Upon cooling to room temperature, evaporated the solvent to give the esters 10a or 10b as red oil. 7.10.1 Step K To a mixture of 400 mL of ethyl alcohol and 200 mL of toluene were added 80 g of intermediate b. Example-7: Preparation of compound of Formula Xlla. Compound of Formula XIa (lOg) and ethanol (50ml) were charged into a round bottom flask at 25-35°C. Reaction mass was heated to reflux and stirred for 2-3hr at and temperature. After completion of the reaction, reaction mass was distilled completely under vacuum at below 50°C and co-distilled with heptane. The resultant reaction mass was stirred with heptane (25ml) for 30min. Filtered the obtained solids and dryed the material to obtain title compound. Yield: 7.0 g; 1H NMR (CDC1The product formed was mixed with ethanol in toluene and heated at 90 C by using reflux condenser for approximately 24 h. The excess ethanol and solvents were removed and progress of reaction was checked by TLC [20]. The final product EFBA was obtained with 52percent yield.

Molecular Weight:210.20
XLogP3:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:210.06922237
Monoisotopic Mass:210.06922237
Topological Polar Surface Area:43.4
Heavy Atom Count:15
Complexity:240
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes