反应详情

温度

92.5 °C

A mixture of intermediate 6, cis-3-{[(tert-butoxycarbonyl)(methyl)amino]methyl}cyclobutyl methanesulfonate (1.5 g, 5.2 mmol), intermediate 18, 3-chloro-5-fluoro-4-(pyrrolidin-1-ylmethyl)phenol (2.38 g, 10.4 mmol) and Cs2CO3 (3.38 g, 10.4 mmol) in DMSO (20 mL) was heated at 90-95° C. for 4 h under vigorous stirring in a flow of argon, then cooled. Water (40 ml) and EtOAc (40 ml) were added, and the layers were separated. The water layer was extracted with ether (20 ml), the combined organic layers were washed with 1N NaOH (3×25 mL), brine, dried with Na2SO4, and evaporated to give the title compound (1.8 g, 82%) as a yellow oil. LC/MS data: 427.6, 429.6, 430.5 (M+H) (calculated for C22H32CFIN2O3 426.96). 1H NMR-data (DMSO-d6): 6.76 (br. s, 1H, Ar—H); 6.71 (dd, 1H, J1=2.2 Hz, J2=11.5 Hz, Ar—H); 4.79-4.92 (m, 1H); 3.65 (s, 2H); 3.32 (d, 2H, J=8.0 Hz); 2.78 (s, 3H, NCH3); 2.38-2.62 (m, 5H+DMSO); 2.20-2.28 (m, 2H); 2.05-2.17 (m, 2H); 1.58-1.73 (m, 4H); 1.41 (s, 9H, Boc).

1. temperaturecooled
2. customthe layers were separated
3. extractionThe water layer was extracted with ether (20 ml)
4. washthe combined organic layers were washed with 1N NaOH (3×25 mL), brine
5. dry with materialdried with Na2SO4
6. customevaporated