4-chlorophthalaldehyde

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DBU (2.36 mL, 15.2 mmol) and methyl{[(benzyloxy)carbonyl]amino}(dimethoxyphosphoryl)acetate (5.02 g, 15.2 mmol) are dissolved in CH2Cl2 (75 mL). The resulting solution is added drop-wise to a solution of 4-chlorophthalaldehyde (2.31 g, 13.8 mmol) in CH2Cl2 (100 mL) at 0° C. The reaction is stirred for 1 hour at 0° C. and then for 18 hours at rt. The volatiles are evaporated to yield a yellow oil, which is dissolved in CHCl3 (10 mL). DBU (2.36 mL, 15.2 mmol) and TFAA (2.15 mL, 15.2 mmol) are added. The reaction is stirred under N2 for 3 hours and is quenched with 150 mL of saturated NaHCO3 solution. The organic layer is separated, and the aqueous layer is extracted with 2×150 mL of CHCl3. The combined organic layers are dried (MgSO4), filtered, and concentrated to a yellow oil. This mixture is purified by column chromatography using a step gradient of 25% to 45% EtOAc in hexanes in 5% increments. Product containing fractions are concentrated, dissolved in MeOH and loaded onto a column of AGW-×2 resin (H+ form). The column is rinsed with MeOH, and the product is eluted with a solution of 5% TEA in MeOH. The product is concentrated from MeOH/MeCN several times to yield methyl 6-chloroisoquinoline-3-carboxylate as a white solid in 67% purity by HPLC (0.810 g). for 18 hours at rt The volatiles are evaporated to yield a yellow oil, which The reaction is stirred under N2 for 3 hours is quenched with 150 mL of saturated NaHCO3 solution The organic layer is separated the aqueous layer is extracted with 2×150 mL of CHCl3 The combined organic layers are dried (MgSO4) filtered concentrated to a yellow oil This mixture is purified by column chromatography Product containing fractions are concentrated dissolved in MeOH The column is rinsed with MeOH the product is eluted with a solution of 5% TEA in MeOH The product is concentrated from MeOH/MeCN several times

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DBU (2.36 mL, 15.2 mmol) and methyl{[(benzyloxy)carbonyl]amino}(dimethoxyphosphoryl)acetate (5.02 g, 15.2 mmol) are dissolved in CH2Cl2 (75 mL). The resulting solution is added drop-wise to a solution of 4-chlorophthalaldehyde (2.31 g, 13.8 mmol) in CH2Cl2 (100 mL) at 0° C. The reaction is stirred for 1 hour at 0° C. and then for 18 hours at rt. The volatiles are evaporated to yield a yellow oil, which is dissolved in CHCl3 (10 mL). DBU (2.36 mL, 15.2 mmol) and TFAA (2.15 mL, 15.2 mmol) are added. The reaction is stirred under N2 for 3 hours and is quenched with 150 mL of saturated NaHCO3 solution. The organic layer is separated, and the aqueous layer is extracted with 2×150 mL of CHCl3. The combined organic layers are dried (MgSO4), filtered, and concentrated to a yellow oil. This mixture is purified by column chromatography using a step gradient of 25% to 45% EtOAc in hexanes in 5% increments. Product containing fractions are concentrated, dissolved in MeOH and loaded onto a column of AGW-×2 resin (H+ form). The column is rinsed with MeOH, and the product is eluted with a solution of 5% TEA in MeOH. The product is concentrated from MeOH/MeCN several times to yield methyl 6-chloroisoquinoline-3-carboxylate as a white solid in 67% purity by HPLC (0.810 g). for 18 hours at rt The volatiles are evaporated to yield a yellow oil, which The reaction is stirred under N2 for 3 hours is quenched with 150 mL of saturated NaHCO3 solution The organic layer is separated the aqueous layer is extracted with 2×150 mL of CHCl3 The combined organic layers are dried (MgSO4) filtered concentrated to a yellow oil This mixture is purified by column chromatography Product containing fractions are concentrated dissolved in MeOH The column is rinsed with MeOH the product is eluted with a solution of 5% TEA in MeOH The product is concentrated from MeOH/MeCN several times

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DBU (2.36 mL, 15.2 mmol) and methyl{[(benzyloxy)carbonyl]amino}(dimethoxyphosphoryl)acetate (5.02 g, 15.2 mmol) are dissolved in CH2Cl2 (75 mL). The resulting solution is added drop-wise to a solution of 4-chlorophthalaldehyde (2.31 g, 13.8 mmol) in CH2Cl2 (100 mL) at 0° C. The reaction is stirred for 1 hour at 0° C. and then for 18 hours at rt. The volatiles are evaporated to yield a yellow oil, which is dissolved in CHCl3 (10 mL). DBU (2.36 mL, 15.2 mmol) and TFAA (2.15 mL, 15.2 mmol) are added. The reaction is stirred under N2 for 3 hours and is quenched with 150 mL of saturated NaHCO3 solution. The organic layer is separated, and the aqueous layer is extracted with 2×150 mL of CHCl3. The combined organic layers are dried (MgSO4), filtered, and concentrated to a yellow oil. This mixture is purified by column chromatography using a step gradient of 25% to 45% EtOAc in hexanes in 5% increments. Product containing fractions are concentrated, dissolved in MeOH and loaded onto a column of AGW-×2 resin (H+ form). The column is rinsed with MeOH, and the product is eluted with a solution of 5% TEA in MeOH. The product is concentrated from MeOH/MeCN several times to yield methyl 6-chloroisoquinoline-3-carboxylate as a white solid in 67% purity by HPLC (0.810 g). for 18 hours at rt The volatiles are evaporated to yield a yellow oil, which The reaction is stirred under N2 for 3 hours is quenched with 150 mL of saturated NaHCO3 solution The organic layer is separated the aqueous layer is extracted with 2×150 mL of CHCl3 The combined organic layers are dried (MgSO4) filtered concentrated to a yellow oil This mixture is purified by column chromatography Product containing fractions are concentrated dissolved in MeOH The column is rinsed with MeOH the product is eluted with a solution of 5% TEA in MeOH The product is concentrated from MeOH/MeCN several times