Ethyl 4-bromoacetoacetate

Control temperature -5 ~ 5 ° C, A mixture of ethyl acetoacetate (26.03 g) was addedWith 15 mL of dichloromethanewell mixed, 35.16 g of bromine was added dropwise, Insulation reaction2h, Pass dry nitrogen lh, After decompression to constant weight, The fraction was collected by distillation at 15 ° C under reduced pressure to obtain a clear oily liquid4 - bromoacetoacetate 3 8.6 9 g, yield 92.54percent;- Formula 147 - Compound 11 aIntermediate B: Ethyl 4-bromo-3-oxobutanoate To a solution of compound A (10.0 g, 76.9 mmol, 1 .0 eq) in acetic acid (30 mL) was added bromine (12.3 g, 76.9 mmol, 1 .0 eq) at 0 °C over 10 min. The mixture was stirred at 0 °C for 1 h, the solvent was removed under reduced pressure and the residue was diluted with water (50 mL). The aqueous mixture was extracted with CHTo a solution of compound A (10.0 g, 76.9 mmol, 1.0 eq) in acetic acid (30 mL) was added bromine (12.3 g, 76.9 mmol, 1.0 eq) at 0° C. over 10 min. 5.0 g (38.4 mmol) of ethyl 3-oxobutanoate were dissolved in 30 ml of acetic acid and cooled to 0° C. 6.15 g (38.4 mmol) of bromine were added slowly and the reaction mixture was then stirred at 0° C. for 2 h. Water was then added, and the reaction mixture was extracted twice with ethyl acetate. The combined organic phases were washed with water and saturated aqueous sodium chloride solution. Drying over sodium sulphate and removal of the solvent gave 6.0 g (75percent of theory) of the intermediate ethyl 4-bromo-3-oxobutanoate as an oil.Intermediate (38) : Preparation of (4-chloro-2-thiophen-2-yl-thieno[2, 3-d] pyrimidin-5-yl)-acetic acid ethyl ester; Step 1. Preparation of 4-bromo-3-oxo-butyric acid ethyl ester; Ethyl acetoacetate (ImI, 7.84mmol) was dissolved in chloroform, therein, bromine(0.6ml, 11.76mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. Sodium sulfite solution was added to quench the reaction, and ethyl acetate was added. Organic layer was washed with water and IN HCl aqueous solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (n-hexane: ethyl acetate = 4:1) to give 800mg (yield: 49percent, colorless oil) of the target compound.[690] A solution of bromine (436 g, 2.73 mol) in acetic acid (750 mL) was added to a solution of ethyl 3-oxobutanoate (355 g, 2.73 mol) in acetic acid (1000 mL). The mixturewas stirred at room temperature for 72 hours and was concentrated under reduced pressure at 45°C to remove the acetic acid. The residue was partitioned between methylene chloride (400 mL) and water (250 mL). The organic layer was washed with saturated sodium bicarbonate (2 x 300 mL), water (300 mL), brine (125 mL) and was dried over anhydrous magnesium sulfate. The solution was filtered and concentrated togive ethyl 4-bromo-3-oxobutanoate as a yellow oil (421 g).73.4 g (1064 mmol) of sodium nitrite, dissolved in 520 ml of water, were added to a solution, stirred at 0° C., of 100 g (769 mmol) of ethyl 3-oxobutanoate in 250 ml of acetic acid. The reaction mixture was stirred at room temperature for 1 h. After addition of water, the mixture was extracted twice with ethyl acetate. The combined organic phases were washed with water and saturated aqueous sodium chloride solution. Drying over sodium sulphate and removal of the solvent gave 105 g (86percent of theory) of the intermediate ethyl 2-(hydroximino)-3-oxobutanoate as a colourless liquid

Molecular Weight:209.04
XLogP3:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:5
Exact Mass:207.97351
Monoisotopic Mass:207.97351
Topological Polar Surface Area:43.4
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes