4-(Bromoacetyl)pyridinehydrobromide

4-Bromoacetyl-pyridine, HBr salt; Dibromine (17.2g, 108 mmol) was added dropwise to a cold (0°C) solution of 4-acetyl- pyridine (12 g, 99 mmol) in acetic acid containing 33percent of HBr (165 mL) under vigourous stirring. The vigorously stirred mixture was warmed to 40°C for 2h and then to 75°C. After 2h at 75°C, the mixture was cooled and diluted with ether (400 mL) to precipitate the product. which was recovered by filtration and washed with ether and acetone to give white crystals (100percent). This material may be recrystallised from methanol and ether.The reaction bottle was added on the batch mother liquor 558g, Additional ethyl acetate 42g, 121.1 g of 4-acetylpyridine was added with stirring, Stir well after 20 ~ 30 ° C batchwise add NBS186.9g;Add temperature slowly warmed to 65 ~ 75 , TLC monitoring of raw materials reaction is completed, cooled to 0 ~ 10 full crystallization.Filtered, washed with 650g deionized water beating, Filtered again, dried to get white275.6 g of 4- (bromoacetyl) pyridine hydrobromide, The molar yield was 98.1percent, To a stirred solution of l-(pyridin-4-yl)-ethanone (10 g, 0.08 mol) in CCl2-Bromo-1 -pyridin-4-ylethanone hydrobromide; To a stirred solution of 4-acetylpyridine (10 mL, 90 mmo.) in glacial acetic acid (40 mL) and 48percent hydrobromic acid (15 mL), bromine (4.65 mL, 90 rnmoS) in giacial acetic acid (10 mL) was added dropwise. After addition, the solution was stirred at room temperature overnight. The white precipitate was filtered off and washed with absolute ethanol, thus obtaining the title compound (22.2 g, 90percent) as a white solid containing traces of dibromoderivative, that was used as such in the next step.Step 1. 2-Bromo-1-lvridin-4-yl-ethanone. To a 0° C. solution of 4-acetylpyridine (4.90 g, 41.3 mmol) and 48percent HBr (7.0 mL) in acetic acid (46.0 mL) was added, dropwise over 15 min, a solution of BrPreparation of 4-Bromoacetylpyridine, HBr saltHBrBromine (24 g, 150 mmol) in 4 mL of 45percent HBr was added drop wise under vigorous stirring to a solution at 70°C of 4-acetyl-pyridine (18 g, 148 mmol) in acetic acid containing 45percent of HBr (165 mL). The vigorously stirred mixture was kept at 70Bromine (131.92 g, 825.49 mmol) was added slowly at room temperature to a stirred solution of 3-1 (100 g, 825.491 mmol) in CC1Intermediate C: Preparation of 2-bromo-l-(pyridin-4-yl)ethanone hydrobromide To a solution of l-(pyridin-4-yl)ethanone (1.0 g, 8.25 mmol) in HO Ac (60 mL) under ice bath was added aqueous HBr (1 mL, 48percent) and BrPreparation of 2-Bromo-l-pyridin-4-yl-ethanone hydrobromide Dibromine (17.2g, 108 mmol) was added drop wise to a cold (OGeneral procedure: Potassium carbonate (418 mg, 3 mmol, 1 eq.) was added to a solution of malonitrile (200 mg, 3 mmol, 1 eq.) in dry DMF (5 mL). The reaction was stirred at room temperature for 1 hour and isopropyl isothiocyanate (311 mL, 3 mmol, 1 eq.) was added. After 1 hour stirring at room temperature, 2-bromo-1-(4-methoxyphenyl)ethan-1-one was added (687 mg, 3 mmol, 1 eq.) followed by potassium carbonate (418 mg, 3 mmol, 1 eq.). The mixture was further stirred for 15 hours, and poured into stirring ice/water (50 mL). The resulting precipitate was filtered and washed with water. The title compound was purified by recristalization from hexane/EtOAc and dried under vaccum (823 mg, yield: 87%, purity: 95.7%, Rt = 1.65 min. by method C).

Molecular Weight:280.94
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:280.88739
Monoisotopic Mass:278.88944
Topological Polar Surface Area:30
Heavy Atom Count:11
Complexity:121
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes