反应详情

To a solution of 1-fluoro-4-((3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(isocyano)methyl)-2-isopropoxybenzene (81 mg, 0.2 mmol) in toluene (2 mL) was added tetrabutylammonium bromide (19 mg, 0.06 mmol) and benzyl bromide (50 mg, 0.22 mmol), followed by 50% KOH(aq) (650 μL). The reaction mixture was vigorously stirred for 3 minutes. The reaction mixture was diluted with EtOAc (20 mL). The organic layer was separated, washed with sat. NaCl (2 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO (12 g silica gel column, 0-40% EtOAc/hexane over 35 min) to yield racemic (±)-methyl 4-(2-(4-fluoro-3-isopropoxyphenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-isocyanoethyl)benzoate as a colorless film (87 mg, 79% yield). LCMS RT=2.24 min [M−NC] 525.1 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); NMR (400 MHz, CDCl3) δ ppm 7.87 (2H, d, J=7.47 Hz), 7.08 (1H, t, J=9.67 Hz), 6.93-6.99 (5H, m), 6.87 (2H, d, J=6.59 Hz), 5.76-6.03 (1H, m), 4.40-4.46 (1H, m), 3.90 (3H, s), 3.65 (2H, s), 1.27 (6H, dd, J=17.58, 5.71 Hz).

1. customThe organic layer was separated
2. washwashed with sat. NaCl (2 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by ISCO (12 g silica gel column, 0-40% EtOAc/hexane over 35 min)