2-(3-氯-4-氟苯胺基)丙-1-醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-[(3-chloro-4-fluorophenyl)amino]propan-1-ol (1-4, 0.030 g, 0.147 mmol) in DCE (1.0 mL) was treated with NaCNBH3 (0.019 g, 0.295 mmol), and 3-hydroxylbenzaldehyde (0.036 g, 0.295 mmol). The resulting mixture stirred at 25° C. for 24 h then concentrated. The reaction was purified by reverse phase liquid chromotography (Semi-prep YMC C-18 Column 5% CH3CN/H2O up to 95% CH3CN/H2O) to give 3-{[(3-chloro-4-fluorophenyl)(2-hydroxy-1-methylethyl)amino]methyl}phenol (1-5). 1H NMR (300 MHz, CDCl3) δ 7.15 (m, 3H), 6.89 (m, 2H), 6.71 (m, 2H), 4.44 (d, J=10.0 Hz, 2H), 4.00 (m, 1H), 3.73 (s, 2H), 1.19 (d, J=6.7 Hz, 3H). MS 310.3 found, 310.7 (M+H+) required. then concentrated The reaction was purified by reverse phase liquid chromotography (Semi-prep YMC C-18 Column 5% CH3CN/H2O up to 95% CH3CN/H2O)

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl N-(3-chloro-4-fluorophenyl)alaninate (1-3, 0.774 g, 3.341 mmol) was treated with DIBAL (6.682 mL, 6.682 mmol) in anhydrous THF (100 mL) at −78° C. The resulting solution was warmed to 25° C. while stirring over 1 h. The resulting solution was treated with a saturated aqueous solution of NH4Cl (1.0 mL) and ether (300 mL) then allowed to stir 30 min. MgSO4 was added and stirred for 20 min then reaction mixture was filtered. The filtrate was concentrated under vacuum to yield 2-[(3-chloro-4-fluorophenyl)amino]propan-1-ol (1-4). 1H NMR (300 MHz, CDCl3) δ 7.26 (s, 1H), 6.94 (dd, J=8.8, 8.8 Hz, 1H), 6.67 (dd, J=6.1, 3.0 Hz, 1H), 6.49 (dd, J=8.8, 5.8, 3.0 Hz, 1H), 3.74 (m, 1H), 3.55 (m, 2H), 1.19 (d, J=6.1 Hz, 3 H). MS 204.2 found, 204.6 (M+H+) required. to stir 30 min stirred for 20 min reaction mixture was filtered The filtrate was concentrated under vacuum