(2-amino-4-methoxyphenyl)methanol

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of commercially available 4-methoxy-2-nitrobenzoic acid (4.0 g, 20.66 mmol) in tetrahydrofuran (20 mL) at −15° C. under nitrogen was added N-methylmorphorine (2.2 ml, 20 mmol) followed by isobutyl chloroformate (2.6 mL, 20 mmol) in portions. After 5 min, the reaction was filtered and the solid was rinsed with tetrahydrofuran (20 mL). The filtrate was cooled to −15° C. and a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate. The reaction was stirred for 5 min. The reaction mixture was partitioned between water and dichloromethane, and extracted aqueous layer with dichloromethane (3×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was redissolved in tetrahydrofuran (35 mL) and added palladium (10% on carbon, 400 mg) and stirred under hydrogen gas for 18 hours. The reaction mixture was then filtered through celite and concentrated under reduced pressure. The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2) gave 744 mg (24% yield) of product as a yellow solid. the reaction was filtered the solid was rinsed with tetrahydrofuran (20 mL) a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate The reaction mixture was partitioned between water and dichloromethane extracted aqueous layer with dichloromethane (3×100 mL) The combined organic layers were washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was redissolved in tetrahydrofuran (35 mL) added palladium (10% on carbon, 400 mg) stirred under hydrogen gas for 18 hours The reaction mixture was then filtered through celite and concentrated under reduced pressure The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2)

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of commercially available 4-methoxy-2-nitrobenzoic acid (4.0 g, 20.66 mmol) in tetrahydrofuran (20 mL) at −15° C. under nitrogen was added N-methylmorphorine (2.2 ml, 20 mmol) followed by isobutyl chloroformate (2.6 mL, 20 mmol) in portions. After 5 min, the reaction was filtered and the solid was rinsed with tetrahydrofuran (20 mL). The filtrate was cooled to −15° C. and a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate. The reaction was stirred for 5 min. The reaction mixture was partitioned between water and dichloromethane, and extracted aqueous layer with dichloromethane (3×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was redissolved in tetrahydrofuran (35 mL) and added palladium (10% on carbon, 400 mg) and stirred under hydrogen gas for 18 hours. The reaction mixture was then filtered through celite and concentrated under reduced pressure. The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2) gave 744 mg (24% yield) of product as a yellow solid. the reaction was filtered the solid was rinsed with tetrahydrofuran (20 mL) a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate The reaction mixture was partitioned between water and dichloromethane extracted aqueous layer with dichloromethane (3×100 mL) The combined organic layers were washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was redissolved in tetrahydrofuran (35 mL) added palladium (10% on carbon, 400 mg) stirred under hydrogen gas for 18 hours The reaction mixture was then filtered through celite and concentrated under reduced pressure The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2)

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

Procedure: A mixture of (2-amino-4-methoxyphenyl)methanol (20 g, 131.0 mmol) and manganese oxide (68 g, 786.0 mmol) in dichloromethane (300 mL) was stirred at RT overnight. LCMS showed the reaction was completed. The solid was filtered off, and the filtrate was concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1) to give the title compound (7 g, 35%) as a yellow solid. MS (ES+) C8H9NO2 requires: 151. found: 152 [M+H]+. The solid was filtered off the filtrate was concentrated The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1)

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

Procedure: A mixture of (2-amino-4-methoxyphenyl)methanol (20 g, 131.0 mmol) and manganese oxide (68 g, 786.0 mmol) in dichloromethane (300 mL) was stirred at RT overnight. LCMS showed the reaction was completed. The solid was filtered off, and the filtrate was concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1) to give the title compound (7 g, 35%) as a yellow solid. MS (ES+) C8H9NO2 requires: 151. found: 152 [M+H]+. The solid was filtered off the filtrate was concentrated The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1)

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

Procedure: To a solution of 2-amino-4-methoxybenzoic acid (15.0 g, 89.8 mmol) in THF (300 mL) was added borohydride in THF (450 mL, 450 mmol) at 0° C., and the reaction mixture was stirred at RT overnight. LCMS showed the reaction was completed. The reaction was quenched with water (150 mL) and extracted with ethyl acetate (500 mL×3). The organic layers were separated, combined, washed with water (200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated to afford the title compound. MS (ES+) C8H11NO2 requires: 153. found: 154 [M+H]+. The reaction was quenched with water (150 mL) extracted with ethyl acetate (500 mL×3) The organic layers were separated washed with water (200 mL) and brine (200 mL) dried over sodium sulfate filtered concentrated

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of commercially available 4-methoxy-2-nitrobenzoic acid (4.0 g, 20.66 mmol) in tetrahydrofuran (20 mL) at −15° C. under nitrogen was added N-methylmorphorine (2.2 ml, 20 mmol) followed by isobutyl chloroformate (2.6 mL, 20 mmol) in portions. After 5 min, the reaction was filtered and the solid was rinsed with tetrahydrofuran (20 mL). The filtrate was cooled to −15° C. and a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate. The reaction was stirred for 5 min. The reaction mixture was partitioned between water and dichloromethane, and extracted aqueous layer with dichloromethane (3×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was redissolved in tetrahydrofuran (35 mL) and added palladium (10% on carbon, 400 mg) and stirred under hydrogen gas for 18 hours. The reaction mixture was then filtered through celite and concentrated under reduced pressure. The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2) gave 744 mg (24% yield) of product as a yellow solid. the reaction was filtered the solid was rinsed with tetrahydrofuran (20 mL) a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate The reaction mixture was partitioned between water and dichloromethane extracted aqueous layer with dichloromethane (3×100 mL) The combined organic layers were washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was redissolved in tetrahydrofuran (35 mL) added palladium (10% on carbon, 400 mg) stirred under hydrogen gas for 18 hours The reaction mixture was then filtered through celite and concentrated under reduced pressure The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2)

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

Procedure: A mixture of (2-amino-4-methoxyphenyl)methanol (20 g, 131.0 mmol) and manganese oxide (68 g, 786.0 mmol) in dichloromethane (300 mL) was stirred at room temperature overnight. The solid was filtered off, and the filtrate was concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1) to give the title compound (7 g, 35%) as a yellow solid. MS (ES+) C8H9NO2 requires: 151, found: 152 [M+H]+. The solid was filtered off the filtrate was concentrated The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1)

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

Procedure: To a solution of 2-amino-4-methoxybenzoic acid (15.0 g, 89.8 mmol) in THF (300 mL) was added borohydride in THF (450 mL, 450 mmol) at 0° C., and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with water (150 mL) and extracted with ethyl acetate (500 mL×3). The organic layers were separated, combined, washed with water (200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated to afford the title compound. MS (ES+) C8H11NO2 requires: 153, found: 154 [M+H]+. The reaction was quenched with water (150 mL) extracted with ethyl acetate (500 mL×3) The organic layers were separated washed with water (200 mL) and brine (200 mL) dried over sodium sulfate filtered concentrated

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

Procedure: A mixture of (2-amino-4-methoxyphenyl)methanol (20 g, 131.0 mmol) and manganese oxide (68 g, 786.0 mmol) in dichloromethane (300 mL) was stirred at room temperature overnight. The solid was filtered off, and the filtrate was concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1) to give the title compound (7 g, 35%) as a yellow solid. MS (ES+) C8H9NO2 requires: 151, found: 152 [M+H]+. The solid was filtered off the filtrate was concentrated The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1)

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

Procedure: To a solution of 2-amino-4-methoxybenzoic acid (15.0 g, 89.8 mmol) in THF (300 mL) was added borohydride in THF (450 mL, 450 mmol) at 0° C., and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with water (150 mL) and extracted with ethyl acetate (500 mL×3). The organic layers were separated, combined, washed with water (200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated to afford the title compound. MS (ES+) C8H11NO2 requires: 153, found: 154 [M+H]+. The reaction was quenched with water (150 mL) extracted with ethyl acetate (500 mL×3) The organic layers were separated washed with water (200 mL) and brine (200 mL) dried over sodium sulfate filtered concentrated

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

Procedure: A mixture of (2-amino-4-methoxyphenyl)methanol (20 g, 131.0 mmol) and manganese oxide (68 g, 786.0 mmol) in dichloromethane (300 mL) was stirred at RT overnight. LCMS showed the reaction was completed. The solid was filtered off, and the filtrate was concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1) to give the title compound (7 g, 35%) as a yellow solid. MS (ES+) C8H9NO2 requires: 151. found: 152 [M+H]+. Synthesis of 2-amino-5-bromo-4-methoxybenzaldehyde The solid was filtered off the filtrate was concentrated The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=6:1)

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

Procedure: To a solution of 2-amino-4-methoxybenzoic acid (15.0 g, 89.8 mmol) in THF (300 mL) was added borohydride in THF (450 mL, 450 mmol) at 0° C., and the reaction mixture was stirred at RT overnight. LCMS showed the reaction was completed. The reaction was quenched with water (150 mL) and extracted with ethyl acetate (500 mL×3). The organic layers were separated, combined, washed with water (200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated to afford the title compound. MS (ES+) C8H11NO2 requires: 153. found: 154 [M+H]+. The reaction was quenched with water (150 mL) extracted with ethyl acetate (500 mL×3) The organic layers were separated washed with water (200 mL) and brine (200 mL) dried over sodium sulfate filtered concentrated