5-溴-2-甲基苯甲醛缩乙二醇

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamine hydrochloride (5.00 g, 19.22 mmol) was taken up in EtOAc and washed with saturated aqueous NaHCO3, water (3×) and brine (2×). The organic layer was dried over MgSO4, filtered and concentrated. To a solution of the residue and bromide INT 31 (6.08 g, 24.99 mmol) in toluene (83 mL) and tert-butanol (33 mL) was added XPhos (1.83 g, 3.84 mmol) followed by Cs2CO3 (18.79 g, 57.67 mmol). The mixture was degassed for 10 minutes and Pd(OAc)2 (0.43 g, 1.92 mmol) was added. The reaction mixture was stirred at 100° C. for 4 hours. The mixture was diluted with EtOAc and washed with H2O (3×). The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine (2×), dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (heptane/EtOAc) to afford INT 32. washed with saturated aqueous NaHCO3, water (3×) and brine (2×) The organic layer was dried over MgSO4 filtered concentrated The mixture was degassed for 10 minutes washed with H2O (3×) The aqueous layer was extracted with EtOAc The combined organic layers were washed with brine (2×) dried over MgSO4 filtered concentrated The residue was purified by chromatography on silica gel (heptane/EtOAc) to afford INT 32

反应条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of INT 30 (17.3 g, 87 mmol) in toluene (505 mL) was added ethane-1,2-diol (24.3 mL, 436 mmol) followed by p-toluenesulfonic acid monohydrate (0.83 g, 4.36 mmol). The reaction mixture was stirred at 130° C. for 21 hours. The mixture was washed with saturated aqueous NaHCO3 (2×) and brine (2×). The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by Kugelrohr distillation to give INT 31. The mixture was washed with saturated aqueous NaHCO3 (2×) and brine (2×) The organic layer was dried over MgSO4 filtered concentrated The residue was purified by Kugelrohr distillation to give INT 31