3-chloro-1-benzofuran-2-carbaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 3-chlorobenzofuran-2-carboxaldehyde (1.62 g, 8.9 mmol) in methanol (50 mL) is added N-methylamine (33% solution in ethanol, 1.11 g, 35.9 mmol) and stirred overnight at room temperature. The mixture is concentrated in vacuo, re-solvated in methanol (50 mL) and cooled in an ice bath. Sodium borohydride (407 mg, 10.8 mmol) is added in portions and the mixture stirred at room temperature for 4 h. The mixture is concentrated in vacuo, re-solvated in 1.3M sodium hydroxide solution, stirred for 20 min, extracted with ethyl acetate, dried with sodium sulfate and concentrated. Purification by column chromatography (silica, CH2Cl2/MeOH, 9/1) gave title compound (1.43 g, 82%) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 7.55-7.63 (m, 2H), 7.33-7.42 (m, 2H), 3.93 (s, 2H), 2.27 (s, 3H). The mixture is concentrated in vacuo, re-solvated in methanol (50 mL) cooled in an ice bath the mixture stirred at room temperature for 4 h The mixture is concentrated in vacuo, re-solvated in 1.3M sodium hydroxide solution stirred for 20 min extracted with ethyl acetate dried with sodium sulfate concentrated Purification by column chromatography (silica, CH2Cl2/MeOH, 9/1)

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

Procedure: To a cooled solution of phosphorus oxychloride (19 mL, 209 mmol) in DMF (40 mL) is slowly added 2-carboxymethoxybenzoic acid (6.84 g, 35 mmol) in portions. The mixture is warmed to room temperature for 30 min and then heated to 90° C. overnight. The mixture is cooled to room temperature and poured carefully into ice water, extracted with ethyl acetate (3×50 mL), dried with sodium sulfate and concentrated in vacuo. Purification by column chromatography (silica, hexanes/ethyl acetate, 4:1) gave title compound (1.62 g, 26%) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 7.82-7.88 (m, 2H), 7.69-7.73 (m, 1H), 5.51-7.56 (m, 1H). heated to 90° C. overnight The mixture is cooled to room temperature extracted with ethyl acetate (3×50 mL) dried with sodium sulfate concentrated in vacuo Purification by column chromatography (silica, hexanes/ethyl acetate, 4:1)

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

Procedure: To a solution of 3-chlorobenzofuran-2-carboxaldehyde (1.62 g, 8.9 mmol) in methanol (50 mL) is added N-methylamine (33% solution in ethanol, 1.11 g, 35.9 mmol) and stirred overnight at room temperature. The mixture is concentrated in vacuo, re-solvated in methanol (50 mL) and cooled in an ice bath. Sodium borohydride (407 mg, 10.8 mmol) is added in portions and the mixture stirred at room temperature for 4 h. The mixture is concentrated in vacuo, re-solvated in 1.3M sodium hydroxide solution, stirred for 20 min, extracted with ethyl acetate, dried with sodium sulfate and concentrated. Purification by column chromatography (silica, CH2Cl2/MeOH, 9/1) gave title compound (1.43 g, 82%) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 7.55-7.63 (m, 2H), 7.33-7.42 (m, 2H), 3.93 (s, 2H), 2.27 (s, 3H). The mixture is concentrated in vacuo, re-solvated in methanol (50 mL) cooled in an ice bath the mixture stirred at room temperature for 4 h The mixture is concentrated in vacuo, re-solvated in 1.3M sodium hydroxide solution stirred for 20 min extracted with ethyl acetate dried with sodium sulfate concentrated Purification by column chromatography (silica, CH2Cl2/MeOH, 9/1)

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

Procedure: To a cooled solution of phosphorus oxychloride (19 mL, 209 mmol) in DMF (40 mL) is slowly added 2-carboxymethoxybenzoic acid (6.84 g, 35 mmol) in portions. The mixture is warmed to room temperature for 30 min and then heated to 90° C. overnight. The mixture is cooled to room temperature and poured carefully into ice water, extracted with ethyl acetate (3×50 mL), dried with sodium sulfate and concentrated in vacuo. Purification by column chromatography (silica, hexanes/ethyl acetate, 4:1) gave title compound (1.62 g, 26%) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 7.82-7.88 (m, 2H), 7.69-7.73 (m, 1H), 5.51-7.56 (m, 1H). heated to 90° C. overnight The mixture is cooled to room temperature extracted with ethyl acetate (3×50 mL) dried with sodium sulfate concentrated in vacuo Purification by column chromatography (silica, hexanes/ethyl acetate, 4:1)