4-溴-2-乙氧基苯胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 62B (2.5 g, 1.2 mmol) in acetonitrile (30 mL) at 0° C. was added dropwise a solution of iodine (6 g, 2.4 mmol), and t-BuONO (1.44 g, 1.4 mmol) in acetonitrile (100 mL) over 30 min and stirred 1.5 h. The mixture was quenched with aqueous Na2SO3 while maintaining the temperature <10° C. After stirring 1 h the mixture was extracted with hexane (3×100 mL). The combined organics were dried (MgSO4) before concentrating in vacuo and the residue was purified by flash chromatography (0-5% EtOAc/Hexane) to afford 62C (2 g, 53%) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (t, J=7.03 Hz, 4 H) 4.06 (q, J=7.03 Hz, 2 H) 6.83 (dd, J=8.35, 1.76 Hz, 1 H) 6.90 (d, J=2.20 Hz, 1 H) 7.59 (d, J=8.35 Hz, 1 H). The mixture was quenched with aqueous Na2SO3 while maintaining the temperature <10° C After stirring 1 h the mixture was extracted with hexane (3×100 mL) The combined organics were dried (MgSO4) before concentrating in vacuo the residue was purified by flash chromatography (0-5% EtOAc/Hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a refluxing solution of 62A (3.0 g, 12.2 mmol), EtOH (60 mL), water (15 mL) and AcOH (10 mL) was added portion-wise Fe powder (5 g, 89.3 mmol) over 30 min. The mixture was heated for 1 h before cooling to ambient temperature and filtering through celite. The filtrate was concentrated in vacuo to afford 62B (2.5 g, 96%) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.42 (t, J=7.03 Hz, 3 H) 4.02 (q, J=6.88 Hz, 2 H) 6.57 (d, J=7.91 Hz, 1 H) 6.85-6.90 (m, 2 H). The mixture was heated for 1 h filtering through celite The filtrate was concentrated in vacuo

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-2-ethoxy-1-nitrobenzene (Preparation 100, 250 mg, 1.016 mmol) in EtOH (15 mL) was added tin (II) chloride (963 mg, 5.08 mmol). The reaction mixture was heated to 70° C. for 2 hours. The reaction mixture was diluted with ice-water (10 mL) and concentrated in vacuo. Aqueous Na2CO3 (2M, 20 mL) was added and the reaction mixture was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by passage through a SCX-2 cartridge eluting with 100% MeOH—1M NH3 in MeOH to give the title compound (179 mg, 82%). concentrated in vacuo Aqueous Na2CO3 (2M, 20 mL) was added the reaction mixture was extracted with EtOAc (3×20 mL) The combined organic layers were washed with brine (30 mL) dried (MgSO4) concentrated in vacuo The residue was purified by passage through a SCX-2 cartridge eluting with 100% MeOH—1M NH3 in MeOH

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Over approximately 1 hour, 3 ml (58.4 mmol) of bromine dissolved in 20 ml of acetic acid is added dropwise to 7.8 ml (60 mmol, 1.03 eq) of 2-ethoxyaniline diluted in 20 ml of acetic acid. When all the bromine has been added, the precipitate formed is filtered on a Buchner funnel and rinsed with acetic acid. The hydrobromide is taken up in H2O, 5 g (90 mmol, 1.5 eq) of KOH pellets is added and extracted with CH2Cl2. The organic phase is dried on MgSO4 and the solvent is evaporated. The residue is purified by column chromatography (eluent CH2Cl2/pentane 9:1) to produce 7.52 g of the expected product as a brown oil (yield: 58%). the precipitate formed is filtered on a Buchner funnel rinsed with acetic acid extracted with CH2Cl2 The organic phase is dried on MgSO4 the solvent is evaporated The residue is purified by column chromatography (eluent CH2Cl2/pentane 9:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 62B (2.5 g, 1.2 mmol) in acetonitrile (30 mL) at 0° C. was added dropwise a solution of iodine (6 g, 2.4 mmol), and t-BuONO (1.44 g, 1.4 mmol) in acetonitrile (100 mL) over 30 min and stirred 1.5 h. The mixture was quenched with aqueous Na2SO3 while maintaining the temperature <10° C. After stirring 1 h the mixture was extracted with hexane (3×100 mL). The combined organics were dried (MgSO4) before concentrating in vacuo and the residue was purified by flash chromatography (0-5% EtOAc/Hexane) to afford 62C (2 g, 53%) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (t, J=7.03 Hz, 4 H) 4.06 (q, J=7.03 Hz, 2 H) 6.83 (dd, J=8.35, 1.76 Hz, 1 H) 6.90 (d, J=2.20 Hz, 1 H) 7.59 (d, J=8.35 Hz, 1 H). The mixture was quenched with aqueous Na2SO3 while maintaining the temperature <10° C After stirring 1 h the mixture was extracted with hexane (3×100 mL) The combined organics were dried (MgSO4) before concentrating in vacuo the residue was purified by flash chromatography (0-5% EtOAc/Hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a refluxing solution of 62A (3.0 g, 12.2 mmol), EtOH (60 mL), water (15 mL) and AcOH (10 mL) was added portion-wise Fe powder (5 g, 89.3 mmol) over 30 min. The mixture was heated for 1 h before cooling to ambient temperature and filtering through celite. The filtrate was concentrated in vacuo to afford 62B (2.5 g, 96%) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.42 (t, J=7.03 Hz, 3 H) 4.02 (q, J=6.88 Hz, 2 H) 6.57 (d, J=7.91 Hz, 1 H) 6.85-6.90 (m, 2 H). The mixture was heated for 1 h filtering through celite The filtrate was concentrated in vacuo