3-Amino-4-chlorobenzaldehyde

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

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

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-3-nitrobenzaldehyde (4.00 mg, 21.6 mmol) in CH2Cl2 (150 mL) at 23° C. was treated with water (50 mL) and N, N′-diheptyl-4,4′-bipyridinium dibromide (220 mg, 10 mg/mmol of substrate). The biphasic mixture was cooled to 5° C. and treated with a solution of sodium dithionite (15.0 g, 86.0 mmol) and K2CO3 (13.4 g, 87.0 mmol) in water (45 mL). The cooling bath was removed and the biphasic mixture stirred vigorously at 23° C. for 4 hours. The mixture was partitioned between additonal CH2Cl2 (75 mL) and water (50 mL) and the aqueous layer was extracted with CH2Cl2 (75 mL). The organic portions were washed with brine (75 mL) and dried (Na2SO4). The residue was treated with ethyl acetate (25 mL) and silica gel (75 g) and the suspension was filtered through a small pad of Celite, rinsing with 10% ethyl acetate/CH2Cl2 (15 mL). The filtrate was concentrated to provide the title compound as an off-yellow powder (3.44 g, 22%). The cooling bath was removed The mixture was partitioned between additonal CH2Cl2 (75 mL) and water (50 mL) the aqueous layer was extracted with CH2Cl2 (75 mL) The organic portions were washed with brine (75 mL) dried (Na2SO4) The residue was treated with ethyl acetate (25 mL) and silica gel (75 g) the suspension was filtered through a small pad of Celite rinsing with 10% ethyl acetate/CH2Cl2 (15 mL) The filtrate was concentrated

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-3-nitrobenzaldehyde (4.00 mg, 21.6 mmol) in CH2Cl2 (150 mL) at 23° C. was treated with water (50 mL) and N, N′-diheptyl-4,4′-bipyridinium dibromide (220 mg, 10 mg/mmol of substrate). The biphasic mixture was cooled to 5° C. and treated with a solution of sodium dithionite (15.0 g, 86.0 mmol) and K2CO3 (13.4 g, 87.0 mmol) in water (45 mL). The cooling bath was removed and the biphasic mixture stirred vigorously at 23° C. for 4 hours. The mixture was partitioned between additonal CH2Cl2 (75 mL) and water (50 mL) and the aqueous layer was extracted with CH2Cl2 (75 mL). The organic portions were washed with brine (75 mL) and dried (Na2SO4). The residue was treated with ethyl acetate (25 mL) and silica gel (75 g) and the suspension was filtered through a small pad of Celite, rinsing with 10% ethyl acetate/CH2Cl2 (15 mL). The filtrate was concentrated to provide the title compound as an off-yellow powder (3.44 g, 22%). The cooling bath was removed The mixture was partitioned between additonal CH2Cl2 (75 mL) and water (50 mL) the aqueous layer was extracted with CH2Cl2 (75 mL) The organic portions were washed with brine (75 mL) dried (Na2SO4) The residue was treated with ethyl acetate (25 mL) and silica gel (75 g) the suspension was filtered through a small pad of Celite rinsing with 10% ethyl acetate/CH2Cl2 (15 mL) The filtrate was concentrated

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

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-4-chlorobenzaldehyde 2 (0.267 g, 1.72 mmol) in DCM (5 mL) at 0° C. was added N-ethyl-N-isopropylpropan-2-amine (0.600 mL, 3.44 mmol) and 5-methylisoxazole-3-carbonyl chloride (0.292 g, 2.01 mmol). The reaction mixture was stirred at 0° C. for 30 min, warmed to room temperature, stirred for 1 h, and diluted with EtOAc. The organic phase was washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 15% to 50% EtOAc in hexanes) gave N-(2-chloro-5-formylphenyl)-5-methylisoxazole-3-carboxamide 3 (0.117 g, 25.8% yield) as a white solid. Mass spectrum: calculated for C12H9ClN2O3 264.0. found 265.0 (M++1). warmed to room temperature stirred for 1 h The organic phase was washed with saturated NaHCO3 (1×), brine (1×) dried over MgSO4 filtered concentrated in vacuo Purification by flash column chromatography on silica gel (eluted with 15% to 50% EtOAc in hexanes)

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

Procedure: To a solution of 4-chloro-3-nitrobenzaldehyde 1 (11.47 g, 62 mmol) in MeOH (230 mL) and water (85 mL) was added ammonium chloride (24.2 g, 452 mmol) and iron (18.4 g, 329 mmol). The reaction mixture was stirred at room temperature for 16 h, filtered, partially concentrated under reduced pressure, and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (3×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. The crude aniline was dissolved in CH2Cl2 (˜150 mL), diluted with hexanes (˜300 mL), and cooled to 0° C. The solid was collected by filtration and washed with hexanes to give 3-amino-4-chlorobenzaldehyde 2 (5.36 g, 56% yield) as a yellow solid. Mass spectrum: calculated for C7H5ClNO 155.0. found 156.1 (M++1). filtered partially concentrated under reduced pressure diluted with EtOAc and water The aqueous phase was extracted with EtOAc (3×) the combined organic extracts were washed with brine (1×) dried over MgSO4 filtered concentrated in vacuo The crude aniline was dissolved in CH2Cl2 (˜150 mL) diluted with hexanes (˜300 mL) cooled to 0° C The solid was collected by filtration washed with hexanes

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-3-nitrobenzaldehyde (4.00 mg, 21.6 mmol) in CH2Cl2 (150 mL) at 23° C. was treated with water (50 mL) and N, N′-diheptyl-4,4′-bipyridinium dibromide (220 mg, 10 mg/mmol of substrate). The biphasic mixture was cooled to 5° C. and treated with a solution of sodium dithionite (15.0 g, 86.0 mmol) and K2CO3 (13.4 g, 87.0 mmol) in water (45 mL). The cooling bath was removed and the biphasic mixture stirred vigorously at 23° C. for 4 hours. The mixture was partitioned between additonal CH2Cl2 (75 mL) and water (50 mL) and the aqueous layer was extracted with CH2Cl2 (75 mL). The organic portions were washed with brine (75 mL) and dried (Na2SO4). The residue was treated with ethyl acetate (25 mL) and silica gel (75 g) and the suspension was filtered through a small pad of Celite, rinsing with 10% ethyl acetate/CH2Cl2 (15 mL). The filtrate was concentrated to provide the title compound as an off-yellow powder (3.44 g, 22%). The cooling bath was removed The mixture was partitioned between additonal CH2Cl2 (75 mL) and water (50 mL) the aqueous layer was extracted with CH2Cl2 (75 mL) The organic portions were washed with brine (75 mL) dried (Na2SO4) The residue was treated with ethyl acetate (25 mL) and silica gel (75 g) the suspension was filtered through a small pad of Celite rinsing with 10% ethyl acetate/CH2Cl2 (15 mL) The filtrate was concentrated