反应详情

To a stirred solution of the mixture of 2-(3-(S)-methoxymethoxypyrrolidin-1-yl)-1-(S)-phenylethanol and 2-(3-(S)-methoxymethoxypyrrolidin-1-yl)-2-(R)-phenylethanol (251 mg, 1.00 mmol) and methylamine (0.167 ml, 1.20 mmol) in CH2Cl2 (4 ml) was added methanesulfonyl chloride (0.093 ml, 1.20 mmol) dropwise at 0° C. (ice bath). After 15.5 h stirring at room temperature, the reaction mixture was washed with saturated NaHCO3 aqueous solution, brine, dried (Na2SO4), and concentrated to give 238 mg of brown viscous oil-(i). To a suspension of NaH (48 mg, 1.20 mmol) in N,N-dimethylformamide (2 ml) was added a solution of 3-chloro-4-methylaminobenzonitrile (200 mg, 1.20 mmol) at room temperature. After stirring for 45 min, to this mixture was added a solution of the above brown viscous oil-(i) in N,N-dimethylformamide (2 ml) at room temperature and the mixture was stirred at room temperature for 4.5 h. H2O was added to this mixture, basified with 25%-NH4OH and extracted with CH2Cl2. The extract was washed with water, brine, dried (Na2SO4), and concentrated to give brown oil, which was purified by column chromatography (silica gel 20 g, CH2C2/MeOH 100/1-50/1) to afford 244 mg (61%) of brown oil.

1. washthe reaction mixture was washed with saturated NaHCO3 aqueous solution, brine
2. dry with materialdried (Na2SO4)
3. concentrationconcentrated
4. customto give 238 mg of brown viscous oil-(i)
5. stirringAfter stirring for 45 min, to this mixture
6. stirringthe mixture was stirred at room temperature for 4.5 h
7. extractionextracted with CH2Cl2
8. washThe extract was washed with water, brine
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated
11. customto give brown oil, which
12. customwas purified by column chromatography (silica gel 20 g, CH2C2/MeOH 100/1-50/1)