2-chloro-6-methylbenzaldehyde

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-chloro-6-methylbenzaldehyde (156 mg, 1.01 mmol), ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoate (434 mg, 1.25 mmol), Pd(PPh3)4 (58 mg, 0.05 mmol), and 2M K3PO4 (aq) (1.0 mL, 2.00 mmol) were dissolved in 1,4-dioxane (3.0 mL) and heated to 100° C. After 4 h the resulting mixture was cooled to room temperature, diluted with DCM, dried (Na2SO4), concentrated and purified via column chromatography to yield the title compound. After 4 h the resulting mixture was cooled to room temperature dried (Na2SO4) concentrated purified via column chromatography

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

Procedure: A 1000 mL, three-necked, round bottomed flask equipped with a magnetic stirrer, thermometer, addition funnel, and argon inlet was charged with 2-chloro-6-methylbenzaldehyde (71.31 g, 461 mmol, crude obtained from the above experiment) and 750 mL of acetonitrile. To this suspension, a solution of monobasic sodium phosphate (115 mmol, 15.9 g) in water 240 mL) was added followed by hydrogen peroxide (50 mL, 30%) at room temperature. Then, a solution of sodium chlorite (73.5 g, 811 mmol) in water (700 mL) was added dropwise at 0° C. while maintaining the temperature below 3° C. After the addition was complete, the yellow suspension was stirred for 15 h at 0° C. to room temperature. TLC analysis of the mixture indicated the absence of starting material. A solution of sodium bisulfite (73 g, 701 mmol) in water (200 mL) was added dropwise at 0° C. until the yellow color disappeared (KI-paper positive). Cooling was maintained throughout to control the exothermic reaction. The solvent was removed under vacuum to afford a colorless solid. The solid was collected by filtration and the filtrate was extracted with diethyl ether (200 mL). The above solid was dissolved in the combined diethyl ether extracts which were then washed with 10% NaOH solution (2×200 mL). The combined aqueous washings were acidified with 10% HCl to pH 1. The resulting colorless precipitate was collected by filtration and air-dried to afford 54.88 g (65%, overall in two steps) of 2-chloro-6-methylbenzoic acid as a colorless solid. A 1000 mL, three-necked, round bottomed flask equipped with a magnetic stirrer thermometer, addition funnel, and argon inlet while maintaining the temperature below 3° C After the addition Cooling was maintained throughout the exothermic reaction The solvent was removed under vacuum to afford a colorless solid The solid was collected by filtration the filtrate was extracted with diethyl ether (200 mL) The above solid was dissolved in the combined diethyl ether extracts which were then washed with 10% NaOH solution (2×200 mL) The resulting colorless precipitate was collected by filtration air-dried

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

Procedure: A 1000 mL, three-necked, round bottomed flask equipped with a magnetic stirrer, thermometer, addition funnel, and argon inlet was charged with 2-chloro-6-methylbenzaldehyde (71.31 g, 461 mmol, crude obtained from the above experiment) and 750 mL of acetonitrile. To this suspension, a solution of monobasic sodium phosphate (115 mmol, 15.9 g) in water 240 mL) was added followed by hydrogen peroxide (50 mL, 30%) at room temperature. Then, a solution of sodium chlorite (73.5 g, 811 mmol) in water (700 mL) was added dropwise at 0° C. while maintaining the temperature below 3° C. After the addition was complete, the yellow suspension was stirred for 15 h at 0° C. to room temperature. TLC analysis of the mixture indicated the absence of starting material. A solution of sodium bisulfite (73 g, 701 mmol) in water (200 mL) was added dropwise at 0° C. until the yellow color disappeared (KI-paper positive). Cooling was maintained throughout to control the exothermic reaction. The solvent was removed under vacuum to afford a colorless solid. The solid was collected by filtration and the filtrate was extracted with diethyl ether (200 mL). The above solid was dissolved in the combined diethyl ether extracts which were then washed with 10% NaOH solution (2×200 mL). The combined aqueous washings were acidified with 10% HCl to pH 1. The resulting colorless precipitate was collected by filtration and air-dried to afford 54.88 g (65%, overall in two steps) of 2-chloro-6-methylbenzoic acid as a colorless solid. A 1000 mL, three-necked, round bottomed flask equipped with a magnetic stirrer thermometer, addition funnel, and argon inlet while maintaining the temperature below 3° C After the addition Cooling was maintained throughout the exothermic reaction The solvent was removed under vacuum to afford a colorless solid The solid was collected by filtration the filtrate was extracted with diethyl ether (200 mL) The above solid was dissolved in the combined diethyl ether extracts which were then washed with 10% NaOH solution (2×200 mL) The resulting colorless precipitate was collected by filtration air-dried

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

Procedure: A 1000 mL, three-necked, round bottomed flask equipped with a magnetic stirrer, thermometer, addition funnel, and argon inlet was charged with 2-chloro-6-methylbenzaldehyde (71.31 g , 461 mmol, crude obtained from the above experiment) and 750 mL of acetonitrile. To this suspension, a solution of monobasic sodium phosphate (115 mmol, 15.9 g) in water 240 mL) was added followed by hydrogen peroxide (50 mL, 30%) at room temperature. Then, a solution of sodium chlorite (73.5 g, 811 mmol) in water (700 mL) was added dropwise at 0° C. while maintaining the temperature below 3° C. After the addition was complete, the yellow suspension was stirred for 15 h at 0° C. to room temperature. TLC analysis of the mixture indicated the absence of starting material. A solution of sodium bisulfite (73 g, 701 mmol) in water (200 mL) was added dropwise at 0° C. until the yellow color disappeared (KI-paper positive). Cooling was maintained throughout to control the exothermic reaction. The solvent was removed under vacuum to afford a colorless solid. The solid was collected by filtration and the filtrate was extracted with diethyl ether (200 mL). The above solid was dissolved in the combined diethyl ether extracts which were then washed with 10% NaOH solution (2×200 mL). The combined aqueous washings were acidified with 10% HCl to pH ˜1. The resulting colorless precipitate was collected by filtration and air-dried to afford 54.88 g (65%, overall in two steps) of 2-chloro-6-methylbenzoic acid as a colorless solid. A 1000 mL, three-necked, round bottomed flask equipped with a magnetic stirrer thermometer, addition funnel, and argon inlet while maintaining the temperature below 3° C After the addition Cooling was maintained throughout the exothermic reaction The solvent was removed under vacuum to afford a colorless solid The solid was collected by filtration the filtrate was extracted with diethyl ether (200 mL) The above solid was dissolved in the combined diethyl ether extracts which were then washed with 10% NaOH solution (2×200 mL) The resulting colorless precipitate was collected by filtration air-dried

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

Procedure: To a stirred solution of 2-chloro-6-methylbenzaldehyde (6.11 g, 39.5 mmol) in THF(2): methanol(3) (30 ml) was added in portion NaBH4 (2.24 g, 59.28 mmol) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 1.3 hours and then quenched with cold sat. NH4Cl solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound. quenched with cold sat. NH4Cl solution extracted with EtOAc dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)

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

Procedure: To a stirred solution of 2-chloro-6-methylbenzaldehyde (6.11 g, 39.5 mmol) in THF(2): methanol(3) (30 ml) was added in portion NaBH4 (2.24 g, 59.28 mmol) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 1.3 hours and then quenched with cold sat. NH4Cl solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound. quenched with cold sat. NH4Cl solution extracted with EtOAc dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-chloro-6-methylbenzaldehyde (156 mg, 1.01 mmol), ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoate (434 mg, 1.25 mmol), Pd(PPh3)4 (58 mg, 0.05 mmol), and 2M K3PO4 (aq) (1.0 mL, 2.00 mmol) were dissolved in 1,4-dioxane (3.0 mL) and heated to 100° C. After 4 h the resulting mixture was cooled to room temperature, diluted with DCM, dried (Na2SO4), concentrated and purified via column chromatography to yield the title compound. After 4 h the resulting mixture was cooled to room temperature dried (Na2SO4) concentrated purified via column chromatography

Conditions: temp:22.01; pressure:0.00; stir:

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

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