反应详情

3-Cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-1-naphthamide (see WO 00/02859; 1.0 g, 2.3 mmol) was dissolved in CH2Cl2 (10 mL) and to the resultant solution were added azetidin-3-ol hydrochloride (0.24 g, 2.2 mmol) and triethylamine (0.30 mL, 2.2 mmol). After stirring for 40 min, sodium triacetoxyborohydride (0.65 g, 3.1 mmol) was added and the solution was stirred at room temperature for 3 h. The solvent was removed by evaporation and the residue was partitioned between saturated aqueous NaHCO3 solution and ethyl acetate. The solvent was removed by evaporation and the residue was dissolved in hydrochloric acid (1M). The solution was washed with CH2Cl2, alkalised with aqueous NaOH (2M) and then extracted with CH2Cl2. The solvent was removed by evaporation and there was obtained 0.85 g (80%) of 3-cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-(3-hydroxyazetidin-1-yl)butyl]-N-methyl-1-naphthamide as a white solid. 1H NMR (400 MHz, DMSO-d6): 0.8-4.4 (cm, 16H), 6.4-8.2 (cm, 8H), 8.6 (d, 1H); LCMS: m/z 482 (M+1)+.

1. stirringthe solution was stirred at room temperature for 3 h
2. customThe solvent was removed by evaporation
3. customthe residue was partitioned between saturated aqueous NaHCO3 solution and ethyl acetate
4. customThe solvent was removed by evaporation
5. dissolutionthe residue was dissolved in hydrochloric acid (1M)
6. washThe solution was washed with CH2Cl2
7. extractionextracted with CH2Cl2
8. customThe solvent was removed by evaporation