potassium;2-ethoxy-2-oxoacetate

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL round-bottomed flask was charged with 7-bromo-2,8-dimethylquinoline (2.0 g, 8.47 mmol), potassium 2-ethoxy-2-oxoacetate (1.98 g, 12.7 mmol) and dcpp-2HBF4 (0.311 g, 0.508 mmol) in anhydrous NMP (28 mL) and nitrogen was bubbled into the mixture for 10 minutes, followed by the addition of Pd(TFA)2 (0.085 g, 0.254 mmol). The mixture was heated at 150° C. in an oil bath under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to ambient temperature and treated with a 2N NaOH solution (20 mL), and the mixture stirred at ambient temperature for 18 hours. The mixture was diluted with water (100 mL) and washed with ethyl acetate (180 mL). The aqueous layer was adjusted to pH 3 with 6N HCl and extracted with a 10% IPA-ethyl acetate solution. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O) to afford 2,8-dimethylquinoline-7-carboxylic acid (0.921 g, 54% yield). was bubbled into the mixture for 10 minutes The reaction mixture was cooled to ambient temperature washed with ethyl acetate (180 mL) extracted with a 10% IPA-ethyl acetate solution The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL round-bottomed flask was charged with 7-bromo-2,8-dimethylquinoline (2.0 g, 8.47 mmol), potassium 2-ethoxy-2-oxoacetate (1.98 g, 12.7 mmol) and dcpp-2HBF4 (0.311 g, 0.508 mmol) in anhydrous NMP (28 mL) and nitrogen was bubbled into the mixture for 10 minutes, followed by the addition of Pd(TFA)2 (0.085 g, 0.254 mmol). The mixture was heated at 150° C. in an oil bath under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to ambient temperature and treated with a 2N NaOH solution (20 mL), and the mixture stirred at ambient temperature for 18 hours. The mixture was diluted with water (100 mL) and washed with ethyl acetate (180 mL). The aqueous layer was adjusted to pH 3 with 6N HCl and extracted with a 10% IPA-ethyl acetate solution. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O) to afford 2,8-dimethylquinoline-7-carboxylic acid (0.921 g, 54% yield). was bubbled into the mixture for 10 minutes The reaction mixture was cooled to ambient temperature washed with ethyl acetate (180 mL) extracted with a 10% IPA-ethyl acetate solution The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL round-bottomed flask was charged with 7-bromo-2,8-dimethylquinoline (2.0 g, 8.47 mmol), potassium 2-ethoxy-2-oxoacetate (1.98 g, 12.7 mmol) and dcpp-2HBF4 (0.311 g, 0.508 mmol) in anhydrous NMP (28 mL) and nitrogen was bubbled into the mixture for 10 minutes, followed by the addition of Pd(TFA)2 (0.085 g, 0.254 mmol). The mixture was heated at 150° C. in an oil bath under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to ambient temperature and treated with a 2N NaOH solution (20 mL), and the mixture stirred at ambient temperature for 18 hours. The mixture was diluted with water (100 mL) and washed with ethyl acetate (180 mL). The aqueous layer was adjusted to pH 3 with 6N HCl and extracted with a 10% IPA-ethyl acetate solution. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O) to afford 2,8-dimethylquinoline-7-carboxylic acid (0.921 g, 54% yield). was bubbled into the mixture for 10 minutes The reaction mixture was cooled to ambient temperature washed with ethyl acetate (180 mL) extracted with a 10% IPA-ethyl acetate solution The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O)

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

Procedure: The procedure of Example 1 was followed using diethyl oxalate (3.0 mL, 22 mmol), potassium trimethylsilanolate (3.85 g, 22 mmol), dry ether (70 mL), an ice bath to maintain room temperature initially, and a 1.5 h reaction time. Potassium ethyl oxalate (2.72 g, 79% yield) was isolated as a white solid: 1H NMR (D2O) δ 1.3 (t, J=7.2 Hz, CH3, 3H), 4.2 ppm (q, J=7.2 Hz, CH2, 2H). Anal. Calcd. for C4H5KO4 : C, 30.76; H, 3.23; K, 25.04. Found: C, 30.39; H, 3.29; K, 25.30. a 1.5 h reaction time

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

Procedure: The procedure of Example 1 was followed using diethyl oxalate (3.0 mL, 22 mmol), potassium trimethylsilanolate (3.85 g, 22 mmol), dry ether (70 mL), an ice bath to maintain room temperature initially, and a 1.5 h reaction time. Potassium ethyl oxalate (2.72 g, 79% yield) was isolated as a white solid: 1H NMR (D2O) δ 1.3 (t, J=7.2 Hz, CH3, 3H), 4.2 ppm (q, J=7.2 Hz, CH2, 2H). Anal. Calcd. for C4H5KO4 : C, 30.76; H, 3.23; K, 25.04. Found: C, 30.39; H, 3.29; K, 25.30. a 1.5 h reaction time

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of potassium monoethyl oxalate (84.3 g; 0.54 mols) in methylene chloride (395 mL) is added dropwise with phosphorous oxychloride (82.8 g; 0.54 mols) keeping the temperature at about 30° C. After 4÷6 hours, 2-(4-methylphenyl)-6-methylimidazo[1,2-a]-pyridine (100.0 g; 0.45 mols) is added, keeping the temperature below 35° C. The resulting suspension is added dropwise with triethylamine (50.5 g; 0.50 mols) keeping the mixture at the reflux temperature. After one hour under these conditions, the reaction mixture is cooled to 5÷10° C. and poured into a suspension of sodium carbonate (95 g; 0.89 mols) in water (500 mL) keeping the temperature below 35° C. The phases are separated and the upper aqueous phase is reextracted with methylene chloride (45 mL). The combined organic phases are washed with water (45 mL) and concentrated to a residue under vacuum. The solid residue is taken up in ethanol (590 mL), heated to dissolution and left to crystallize. After cooling to about 0° C. the solid is filtered, washed with ethanol and dried at 50° C. under vacuum to obtain ethyl 2-(4-methylphenyl)-6-methylimidazo[1,2-a]-pyridine-3-glyoxalate (141.5 g, 99.5% titre, 97.5% yield). at about 30° C the temperature below 35° C the temperature below 35° C The phases are separated The combined organic phases are washed with water (45 mL) concentrated to a residue under vacuum heated to dissolution left to crystallize After cooling to about 0° C. the solid is filtered washed with ethanol dried at 50° C. under vacuum

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of potassium bicarbonate (100 g; 1.00 mols) in diethyl oxalate (146.1 g; 1.00 mols) is added with water (26 g) and heated at a temperature of 50÷55° C. for 6÷8 hours until carbon dioxide evolution ceases. The suspension is cooled to 40° C., added with acetone (250 mL) and cooled to 15÷20° C. The resulting solid is filtered, washed with acetone (2×25 mL) and dried at 50° C. under vacuum to obtain potassium monoethyl oxalate (150.0 g, 99% purity, yield 96%). cooled to 15÷20° C The resulting solid is filtered washed with acetone (2×25 mL) dried at 50° C. under vacuum

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL round-bottomed flask was charged with 7-bromo-2,8-dimethylquinoline (2.0 g, 8.47 mmol), potassium 2-ethoxy-2-oxoacetate (1.98 g, 12.7 mmol) and dcpp-2HBF4 (0.311 g, 0.508 mmol) in anhydrous NMP (28 mL) and nitrogen was bubbled into the mixture for 10 minutes, followed by the addition of Pd(TFA)2 (0.085 g, 0.254 mmol). The mixture was heated at 150° C. in an oil bath under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to ambient temperature and treated with a 2N NaOH solution (20 mL), and the mixture stirred at ambient temperature for 18 hours. The mixture was diluted with water (100 mL) and washed with ethyl acetate (180 mL). The aqueous layer was adjusted to pH 3 with 6N HCl and extracted with a 10% IPA-ethyl acetate solution. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O) to afford 2,8-dimethylquinoline-7-carboxylic acid (0.921 g, 54% yield). was bubbled into the mixture for 10 minutes The reaction mixture was cooled to ambient temperature washed with ethyl acetate (180 mL) extracted with a 10% IPA-ethyl acetate solution The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O)

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

Procedure: The procedure of Example 1 was followed using diethyl oxalate (3.0 mL, 22 mmol), potassium trimethylsilanolate (3.85 g, 22 mmol), dry ether (70 mL), an ice bath to maintain room temperature initially, and a 1.5 h reaction time. Potassium ethyl oxalate (2.72 g, 79% yield) was isolated as a white solid: 1H NMR (D2O) δ 1.3 (t, J=7.2 Hz, CH3, 3H), 4.2 ppm (q, J=7.2 Hz, CH2, 2H). Anal. Calcd. for C4H5KO4 : C, 30.76; H, 3.23; K, 25.04. Found: C, 30.39; H, 3.29; K, 25.30. a 1.5 h reaction time