2-Bromo-2-(2-fluorophenyl)-1-cycloprop...

The 1-cyclopropyl-2 - (2-fluoro phenyl) - 2-ethyl ketone 17.8g (100mmol), iodine monobromide 62g (300mmol) and 1-butyl-3- methyl bromination imidazole ium 8.7g (40mmol) in 150 ml anhydrous tetrahydrofuran in 40 °C contact reaction 4 hours, after the reaction, cooling to room temperature, into ice water, ethyl acetate extraction, saturated sodium bisulfite washing, organic phase is concentrated, recrystallized with ethanol to obtain 1-cyclopropyl-2-bromo-2 - (2-fluoro phenyl) - 2-ethyl ketone 24.5g, yield of 95.3percent, purity 99.73percent.150 g of cyclopropyl-2-fluorobenzyl ketone and 1.8 1 of methanol were mixed in a 10- liter 4-neck flask fitted with condenser. Subsequently, 147.9 g of liquid bromine were added dropwise to the mixture over a period of 3.5 hours, which was further stirred for 2.5 hours at 25-30 °C. Afterwards, the mixture was cooled down to 10 °C and 3.8 1 of pre chilled water added dropwise to the reactor. The reaction mass was extracted with 2.25 1 of ethyl acetate and the organic and the aqueous layer separated. The aqueous layer was extracted with 750 ml of ethyl acetate. Successively the layers were separated and the ethyl acetate layers were mixed and washed with 750 ml of a 10percent w/v solution of sodium metabisulphite. The layers were separated and the ethyl acetate layer was washed with 750 ml of a 10percent w/v solution of sodium bicarbonate. Afterwards, the layers were separated and the ethyl acetate layer was washed with 750 ml of brine solution. Lastly, the ethyl acetate layer was separated and was dried over 100 g of sodium sulphate and concentrated under vacuum at 50-55 °C to yield 205 g of the title compound as a yellow coloured oil. Yield: 94.65percent. Purity (HPLC): 95.76percentExample-2; Preparation of 2-bromo-l-cyclopropyl-2-(2-fluorophenyl) ethanone (III); To a solution of l-cyclopropyl-2-(2-fluorophenyl) ethanone (3.0 gm) in cyclohexane (60 ml) was added DBDMH (7.2 gm) and AIBN (0.27 g) and then the mixture was heated under reflux for 3 hours. The reaction mass was cooled to 10°C and stirred for 2 hours and was filtered off to remove unwanted solid. The filtrate was washed with 5percent sodium metabisulphite, water and sodium bicarbonate solution, and then concentrated under reduced pressure to afford 2-bromo-l-cyclopropyl-2-(2-fluorophenyl) ethanone (4.03 g Yield = 93.28percent) as a oil.Prasugrel intermediate 1-cyclopropyl -2 bromo-2 - (2-fluoro phenyl) - 2-ethanone synthesis of The 1-cyclopropyl-2 - (2-fluoro phenyl) - 2-ethyl ketone 29.1g (10mmol) with bromine (20mmol) in the tetrahydrofuran 20 °C reaction 10 hours, after the reaction, cooling to room temperature, into ice water, dichloromethane extraction, saturated sodium bisulfite washing, organic phase is concentrated, anhydrous methanol is recrystallized to get pulls Grey intermediate 1-cyclopropyl-2-bromo-2 - (2-fluoro phenyl) - 2-ethyl ketone 2.3g, the yield is 90.4percent, purity of 99.86percent.8.9 g of cyclopropyl-2-(2-fluorophenyl)ethanone was dissolved in 80 ml of chloroform.Add three reaction flasks, add 8percent of azobisisobutyronitrile, and add 9.6g of NBS in batches under stirring.After the addition was completed at 20°C for 8 hours, the other steps were the same as in to obtain 10.7 g of compound (V) in a yield of 83.2percent and HPLC: >96.4percent.Example 32-bromo-l-cycIopropyI-2-(2-fluorophenyI)-ethanone (compound of the Formula (III) )4.0 g of l-cyclopropyl-2-(2-fluorophenyl)-ethanone having 98.0percent content according to gas chromatographic analysis is introduced into a 100-ml round-bottom flask and 0.4 g of p-toluenesulfonic acid monohydrate are added. The mixture is heated to 80 °C and at the same temperature, 3.8 g of N-bromosuccinimide are added. After the reaction is complete, the mixture is cooled to a temperature between 20 and 25 °C. 18 g of 5 percent by weight sodium hydroxide solution and 30 ml of methyl-t-butylether are added. The mixture is stirred for 10 minutes and subsequently the layers are separated. The organic layer is washed twice with 20 ml of water each and the organic layer is evaporated.Yield of the raw product: 5.7 g (pure: 4.5 g, 78percent), pale yellow liquid. Assay (measured by gas chromatography) 79.3percentIn a 250 ml round-bottomed flask a solution of cyclopropyl-2-fluorbenzyl ketone (8.91 g, 50 mmol), ethanol (50 ml), aqueous hydrogen peroxide solution (30 wpercent, 30 ml, 0.29 mol) and aqueous hydrogen bromide solution (48 wpercent, 22.6 ml, 0.20 mol) are added. The reaction mixture is boiled for half an hour and the colourless solution is evaporated. To the residue water (50 ml) and ethyl acetate (50 ml) are added at 25 °C, the phases are separated and the organic phase is dried and evaporated.The obtained product: 9.4 g light yellow oil Yield: 73.8 percentContent (measured by GC/MS): In a 250 ml round-bottomed flask a solution of cyclopropyl-2-fluorbenzyl ketone (8.91 g, 50 mmol), 7V-benzyl-triethyl-ammonium bromide (2.0 g), aqueous hydrogen peroxide solution (30 wpercent, 40 ml, 0.39 mol) and aqueous hydrogen bromide solution (48 wpercent, 28.3 ml, 0.25 mol) are added. The reaction mixture is stirred intensively for two hours at 85

Molecular Weight:257.10
XLogP3:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:255.98991
Monoisotopic Mass:255.98991
Topological Polar Surface Area:17.1
Heavy Atom Count:14
Complexity:227
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes