(2-amino-4,5-difluorophenyl)methanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Trimethylacetyl chloride (4.01 mL, 32.55 mmol) was added to the solution of the crude (2-amino-4,5-difluorophenyl)methanol in CH2Cl2/THF (50 mL/10 mL) at 0° C., followed by the addition of DIEA (10.8 mL, 62 mmol). The resulting mixture was stirred for 30 min, and then partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL). After separation, the organic phase was washed with brine (40 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected product, which was pure enough to be used in next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 9 H), 4.62 (s, 2 H), 6.94 (dd, J=10.20, 8.44 Hz, 1 H), 8.08 (dd, J=12.72, 7.68 Hz, 1 H), 9.04 (s, 1 H); Mass spec. 244.11 (MH+), Calc. for C12H15F2NO2 243.11. partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL) After separation the organic phase was washed with brine (40 mL) dried over MgSO4 concentrated on rotary vacuum

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

実験手順: 2-Amino-4,5-difluorobenzoic acid (5.37 g, 31.0 mmol) in THF (50 mL) was dropwise added to the suspension on LAH (1.65 g, 43.5 mmol) in THF (15 mL) at room temperature under N2 over 10 min. The resulting suspension was stirred at room temperature for 1 hr. Then the mixture was cooled down to 0° C., quenched with saturated Na2SO4 (100 mL), and extracted with Et2O (2×100 mL), the combined organic layers were washed with brine (60 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected crude product as a brown solid, which was pure enough to be used in next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 1 H), 4.56 (s, 2 H), 6.46 (dd, J=11.71, 6.92 Hz, 1 H), 6.87 (dd, J=10.58, 8.56 Hz, 1 H); Mass spec. 160.04 (MH+), Calc. for C7H7F2NO 159.05. Then the mixture was cooled down to 0° C. quenched with saturated Na2SO4 (100 mL) extracted with Et2O (2×100 mL) the combined organic layers were washed with brine (60 mL) dried over MgSO4 concentrated on rotary vacuum

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

実験手順: Trimethylacetyl chloride (4.01 mL, 32.55 mmol) was added to the solution of the crude (2-amino-4,5-difluorophenyl) methanol in CH2Cl2/THF (50 mL/10 mL) at 0° C., followed by the addition of DIEA (10.8 mL, 62 mmol). The resulting mixture was stirred for 30 min, and then partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL). After separation, the organic phase was washed with brine (40 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected product, which was pure enough to be used in next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 9 H), 4.62 (s, 2 H), 6.94 (dd, J=10.20, 8.44 Hz, 1 H), 8.08 (dd, J=12.72, 7.68 Hz, 1 H), 9.04 (s, 1 H); Mass spec. 244.11 (MH+), Calc. for C12H15F2NO2 243.11. partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL) After separation the organic phase was washed with brine (40 mL) dried over MgSO4 concentrated on rotary vacuum

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

実験手順: 2-Amino-4,5-difluorobenzoic acid (5.37 g, 31.0 mmol) in THF (50 mL) was dropwise added to the suspension on LAH (1.65 g, 43.5 mmol) in THF (15 mL) at room temperature under N2 over 10 min. The resulting suspension was stirred at room temperature for 1 hr. Then the mixture was cooled down to 0° C., quenched with saturated Na2SO4 (100 mL), and extracted with Et2O (2×100 mL), the combined organic layers were washed with brine (60 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected crude product as a brown solid, which was pure enough to be used in next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 1 H), 4.56 (s, 2 H), 6.46 (dd, J=11.71, 6.92 Hz, 1 H), 6.87 (dd, J=10.58, 8.56 Hz, 1 H); Mass spec. 160.04 (MH+), Calc. for C7H7F2NO 159.05. Then the mixture was cooled down to 0° C. quenched with saturated Na2SO4 (100 mL) extracted with Et2O (2×100 mL) the combined organic layers were washed with brine (60 mL) dried over MgSO4 concentrated on rotary vacuum

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Trimethylacetyl chloride (4.01 mL, 32.55 mmol) was added to the solution of the crude (2-amino-4,5-difluorophenyl)methanol in CH2Cl2/THF (50 mL/10 mL) at 0° C., followed by the addition of DIEA (10.8 mL, 62 mmol). The resulting mixture was stirred for 30 min, and then partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL). After separation, the organic phase was washed with brine (40 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected product, which was pure enough to be used in next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 9 H), 4.62 (s, 2 H), 6.94 (dd, J=10.20, 8.44 Hz, 1 H), 8.08 (dd, J=12.72, 7.68 Hz, 1 H), 9.04 (s, 1 H); Mass spec. 244.11 (MH+), Calc. for C12H15F2NO2 243.11. partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL) After separation the organic phase was washed with brine (40 mL) dried over MgSO4 concentrated on rotary vacuum

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

実験手順: 2-Amino-4,5-difluorobenzoic acid (5.37 g, 31.0 mmol) in THF (50 mL) was dropwise added to the suspension on LAH (1.65 g, 43.5 mmol) in THF (15 mL) at room temperature under N2 over 10 min. The resulting suspension was stirred at room temperature for 1 hr. Then the mixture was cooled down to 0° C., quenched with saturated Na2SO4 (100 mL), and extracted with Et2O (2×100 mL), the combined organic layers were washed with brine (60 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected crude product as a brown solid, which was pure enough to be used in next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 1 H), 4.56 (s, 2 H), 6.46 (dd, J=11.71, 6.92 Hz, 1 H), 6.87 (dd, J=10.58, 8.56 Hz, 1 H); Mass spec. 160.04 (MH+), Calc. for C7H7F2NO 159.05. Then the mixture was cooled down to 0° C. quenched with saturated Na2SO4 (100 mL) extracted with Et2O (2×100 mL) the combined organic layers were washed with brine (60 mL) dried over MgSO4 concentrated on rotary vacuum

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

実験手順: Trimethylacetyl chloride (4.01 mL, 32.55 mmol) was added to the solution of the crude (2-amino-4,5-difluorophenyl) methanol in CH2Cl2/THF (50 mL/10 mL) at 0° C., followed by the addition of DIEA (10.8 mL, 62 mmol). The resulting mixture was stirred for 30 min, and then partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL). After separation, the organic phase was washed with brine (40 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected product, which was pure enough to be used in next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 9 H), 4.62 (s, 2 H), 6.94 (dd, J=10.20, 8.44 Hz, 1 H), 8.08 (dd, J=12.72, 7.68 Hz, 1 H), 9.04 (s, 1 H); Mass spec. 244.11 (MH+), Calc. for C12H15F2NO2 243.11. partitioned between saturated NaHCO3(100 mL) and CH2Cl2 (150 mL) After separation the organic phase was washed with brine (40 mL) dried over MgSO4 concentrated on rotary vacuum

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

実験手順: 2-Amino-4,5-difluorobenzoic acid (5.37 g, 31.0 mmol) in THF (50 mL) was dropwise added to the suspension on LAH (1.65 g, 43.5 mmol) in THF (15 mL) at room temperature under N2 over 10 min. The resulting suspension was stirred at room temperature for 1 hr. Then the mixture was cooled down to 0° C., quenched with saturated Na2SO4 (100 mL), and extracted with Et2O (2×100 mL), the combined organic layers were washed with brine (60 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected crude product as a brown solid, which was pure enough to be used in next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 1 H), 4.56 (s, 2 H), 6.46 (dd, J=11.71, 6.92 Hz, 1 H), 6.87 (dd, J=10.58, 8.56 Hz, 1 H); Mass spec. 160.04 (MH+), Calc. for C7H7F2NO 159.05. Then the mixture was cooled down to 0° C. quenched with saturated Na2SO4 (100 mL) extracted with Et2O (2×100 mL) the combined organic layers were washed with brine (60 mL) dried over MgSO4 concentrated on rotary vacuum

反応条件: temp:0.00; pressure:0.00; stir: