ethyl 2-bromo-3-oxo-3-phenylpropanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl benzoylacetate (0.27 mL, 1.6 mmol) [Fluka cat#12990] was dissolved in dimethyl sulfoxide (5.0 mL) at room temperature and the N-bromosuccinimide (0.30 g, 1.7 mmol) was added portion wise. The reaction mixture was stirred for 3 h and EtOAc was added and washed with water, water saturated sodium bicarbonate, brine, dried over magnesium sulfate and concentrated to give Ethyl 2-bromo-3-oxo-3-phenylpropanoate (0.40 g, 95%) as an oil %). LCMS calc. for C11H12BrO3 (M+H)+: m/z=271.0, 273.0. found: 271.0, 273.0. washed with water, water saturated sodium bicarbonate, brine dried over magnesium sulfate concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of benzoylacetic acid, ethyl ester (0.01 mol) in a solvent such as, for example, chloroform is added N-bromosuccinimide (NBS, 0.01 mol), and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of benzoyl-bromoacetic acid, ethyl ester is formed, ethyl acetate is added, and the mixture is rotary evaporated to remove chloroform. To the resulting ethyl acetate mixture is added thiocarbamic acid, benzyl ester, which may be prepared as described in Step (a) above, and a suitable non-nucleophilic base such as those described in Example 17 above, and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of the desired product is formed, the reaction is washed with 0.01 M hydrochloric acid, water, brine, and dried over sodium sulfate. The mixture is rotary evaporated to give 2-benzyloxy-4-phenyl-thiazol-5-carboxylic acid, ethyl ester, which may be purified, if needed or desired, by chromatography on silica gel or crystallization. Reaction progress

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of benzoylacetic acid, ethyl ester (0.01 mol) in a solvent such as, for example, chloroform is added N-bromosuccinimide (NBS, 0.01 mol), and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of benzoyl-bromoacetic acid, ethyl ester is formed, ethyl acetate is added, and the mixture is rotary evaporated to remove chloroform. To the resulting ethyl acetate mixture is added thiocarbamic acid, benzyl ester, which may be prepared as described in Step (a) above, and a suitable non-nucleophilic base such as those described in Example 17 above, and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of the desired product is formed, the reaction is washed with 0.01 M hydrochloric acid, water, brine, and dried over sodium sulfate. The mixture is rotary evaporated to give 2-benzyloxy-4-phenyl-thiazol-5-carboxylic acid, ethyl ester, which may be purified, if needed or desired, by chromatography on silica gel or crystallization. Reaction progress

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of commercially available pyrazolo[1,5-a]pyridine-3-carbothioamide (580 mg, 3.3 mmol) in ethanol (20 mL) was added ethyl 2-bromo-3-oxo-3-phenylpropanoate (1.0 g, 3.7 mmol), and the mixture was heated under reflux for 11 hr. The reaction solution was allowed to cool to room temperature, and the resulting solid was collected by filtration and washed with methanol. The collected filtrate and washing solution was concentrated under reduced pressure, and the obtained residue was suspended in ethyl acetate (100 mL). The obtained suspension was washed with saturated aqueous sodium bicarbonate solution (50 mL×2), and the collected aqueous layer was extracted with ethyl acetate (50 mL). The collected organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→100/0) to give the title compound (360 mg, 31%) as a yellow solid. the mixture was heated under reflux for 11 hr the resulting solid was collected by filtration washed with methanol The collected filtrate and washing solution was concentrated under reduced pressure The obtained suspension was washed with saturated aqueous sodium bicarbonate solution (50 mL×2) the collected aqueous layer was extracted with ethyl acetate (50 mL) The collected organic layer was dried over anhydrous magnesium sulfate the insoluble material was filtered off the filtrate was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→100/0)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of pyridine-4-carbothioamide (2.9 g, 21 mmol) in ethanol (150 mL) was added ethyl 2-bromo-3-oxo-3-phenylpropanoate (5.9 g, 22 mmol), and the mixture was heated under reflux for 8 hr. The reaction solution was allowed to cool to room temperature, and the solid was collected by filtration, washed with diethyl ether, dried, suspended in ethyl acetate (250 mL), and washed with saturated aqueous sodium bicarbonate solution (150 mL×2). The combined aqueous layer was extracted with ethyl acetate (100 mL×2). The combined organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was washed with diethyl ether, and collected by filtration to give the title compound (3.7 g, 57%) as a colorless solid. the mixture was heated under reflux for 8 hr the solid was collected by filtration washed with diethyl ether dried washed with saturated aqueous sodium bicarbonate solution (150 mL×2) The combined aqueous layer was extracted with ethyl acetate (100 mL×2) The combined organic layer was dried over anhydrous magnesium sulfate the insoluble material was filtered off the filtrate was concentrated under reduced pressure The residue was washed with diethyl ether collected by filtration

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25 ml (0.144 mol) of ethyl benzoyl acetate are dissolved in 50 ml of CCl4, 8.5 ml of bromine are added dropwise at 5° C. and the brown solution is stirred at 5° C. for 1 h, at room temperature for 3 h and at 60° C. for 2 h. It is concentrated to dryness, the residue is taken up in EA, the EA solution is washed with 10% strength Na2SO3 solution and satd. NaCl solution, dried over MgSO4 and concentrated, and the residue is dried in a high vacuum. 38 g of the title compound result as a red oil. It is concentrated to dryness the EA solution is washed with 10% strength Na2SO3 solution NaCl solution, dried over MgSO4 concentrated the residue is dried in a high vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25 ml (0.144 mol) of ethyl benzoyl acetate are dissolved in 50 ml of CCl4, 8.5 ml of bromine are added dropwise at 5° C. and the brown solution is stirred at 5° C. for 1 h, at room temperature for 3 h and at 60° C. for 2 h. It is concentrated to dryness, the residue is taken up in EA, the EA solution is washed with 10% strength Na2SO3 solution and satd. NaCl solution, dried over MgSO4 and concentrated, and the residue is dried in a high vacuum. 38 g of the title compound result as a red oil. It is concentrated to dryness the EA solution is washed with 10% strength Na2SO3 solution NaCl solution, dried over MgSO4 concentrated the residue is dried in a high vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of commercially available pyrazolo[1,5-a]pyridine-3-carbothioamide (580 mg, 3.3 mmol) in ethanol (20 mL) was added ethyl 2-bromo-3-oxo-3-phenylpropanoate (1.0 g, 3.7 mmol), and the mixture was heated under reflux for 11 hr. The reaction solution was allowed to cool to room temperature, and the resulting solid was collected by filtration and washed with methanol. The collected filtrate and washing solution was concentrated under reduced pressure, and the obtained residue was suspended in ethyl acetate (100 mL). The obtained suspension was washed with saturated aqueous sodium bicarbonate solution (50 mL×2), and the collected aqueous layer was extracted with ethyl acetate (50 mL). The collected organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→100/0) to give the title compound (360 mg, 31%) as a yellow solid. the mixture was heated under reflux for 11 hr the resulting solid was collected by filtration washed with methanol The collected filtrate and washing solution was concentrated under reduced pressure The obtained suspension was washed with saturated aqueous sodium bicarbonate solution (50 mL×2) the collected aqueous layer was extracted with ethyl acetate (50 mL) The collected organic layer was dried over anhydrous magnesium sulfate the insoluble material was filtered off the filtrate was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→100/0)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of pyridine-4-carbothioamide (2.9 g, 21 mmol) in ethanol (150 mL) was added ethyl 2-bromo-3-oxo-3-phenylpropanoate (5.9 g, 22 mmol), and the mixture was heated under reflux for 8 hr. The reaction solution was allowed to cool to room temperature, and the solid was collected by filtration, washed with diethyl ether, dried, suspended in ethyl acetate (250 mL), and washed with saturated aqueous sodium bicarbonate solution (150 mL×2). The combined aqueous layer was extracted with ethyl acetate (100 mL×2). The combined organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was washed with diethyl ether, and collected by filtration to give the title compound (3.7 g, 57%) as a colorless solid. the mixture was heated under reflux for 8 hr the solid was collected by filtration washed with diethyl ether dried washed with saturated aqueous sodium bicarbonate solution (150 mL×2) The combined aqueous layer was extracted with ethyl acetate (100 mL×2) The combined organic layer was dried over anhydrous magnesium sulfate the insoluble material was filtered off the filtrate was concentrated under reduced pressure The residue was washed with diethyl ether collected by filtration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl benzoylacetate (0.27 mL, 1.6 mmol) [Fluka cat#12990] was dissolved in dimethyl sulfoxide (5.0 mL) at room temperature and the N-bromosuccinimide (0.30 g, 1.7 mmol) was added portion wise. The reaction mixture was stirred for 3 h and EtOAc was added and washed with water, water saturated sodium bicarbonate, brine, dried over magnesium sulfate and concentrated to give Ethyl 2-bromo-3-oxo-3-phenylpropanoate (0.40 g, 95%) as an oil %). LCMS calc. for C11H12BrO3 (M+H)+: m/z=271.0, 273.0. found: 271.0, 273.0. washed with water, water saturated sodium bicarbonate, brine dried over magnesium sulfate concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of benzoylacetic acid, ethyl ester (0.01 mol) in a solvent such as, for example, chloroform is added N-bromosuccinimide (NBS, 0.01 mol), and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of benzoyl-bromoacetic acid, ethyl ester is formed, ethyl acetate is added, and the mixture is rotary evaporated to remove chloroform. To the resulting ethyl acetate mixture is added thiocarbamic acid, benzyl ester, which may be prepared as described in Step (a) above, and a suitable non-nucleophilic base such as those described in Example 17 above, and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of the desired product is formed, the reaction is washed with 0.01 M hydrochloric acid, water, brine, and dried over sodium sulfate. The mixture is rotary evaporated to give 2-benzyloxy-4-phenyl-thiazol-5-carboxylic acid, ethyl ester, which may be purified, if needed or desired, by chromatography on silica gel or crystallization. Reaction progress