反应详情

(2S)-3-(4-Cyano-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide was prepared as described in Example 3 starting from 2-fluoro-4-hydroxybenzonitrile and (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide according to the following procedure. A solution of 2-fluoro-4-hydroxybenzonitrile (0.2 g, 1.4 mmol), (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide (0.37 g, 1.2 mmol), K2CO3 (0.34 g, 2.5 mmol) and benzyltriethylammonium chloride (0.028 g, 0.1 mmol) in methyl ethyl ketone (40 ml) was refluxed for 5 hours. The mixture was cooled to the room temperature and evaporated. The residue was partitioned between ethyl acetate (50 ml) and water (50 ml) and the phases were separated. The organic phase was washed with 1 M Na2CO3 (4×20 ml) and water (1×20 ml), dried over Na2SO4 and evaporated. The crude product was purified by flash chromatography (eluent CH2Cl2). 1H NMR (DMSO-d6): 1.46 (3H, s), 2.53 (3H, s), 4.11 (1H, d, J=10.1 Hz), 4.371 (1H, d, J=10.1 Hz), 6.33 (1H, bs), 6.96 (1H, m), 7.18 (1H, m), 7.80 (1H, m), 7.88 (1H, dd, J=9.0 Hz and 2.1 Hz), 7.91 (1H, d, J=2.1 Hz), 8.03 (1H, d, J=9.0 Hz) 10.21 (1H, s).

1. customevaporated
2. customThe residue was partitioned between ethyl acetate (50 ml) and water (50 ml)
3. customthe phases were separated
4. washThe organic phase was washed with 1 M Na2CO3 (4×20 ml) and water (1×20 ml)
5. dry with materialdried over Na2SO4
6. customevaporated
7. customThe crude product was purified by flash chromatography (eluent CH2Cl2)