反应详情

3-(4-Bromophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.64 g, 1.7 mmol), 1-methanesulfonylpiperazine (0.43 g, 2.6 mmol), tris-(dibenzylideneacetone)dipalladium (0.069 g, 0.07 mmol), S-Phos (0.11 g, 0.28 mmol), and sodium t-butoxide (0.25 g, 2.6 mmol) are placed in 10 ml of toluene under nitrogen. The reaction medium is stirred at reflux for 1 h 30. After hydrolysis with a saturated aqueous NaHCO3 solution, and extraction with ethyl acetate, the organic phase is washed with a saturated aqueous sodium chloride solution and dried over MgSO4. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol/ethyl acetate in dichloromethane ranging from 100/0/0 to 7/2.5/0.5 (dichloromethane/ethyl acetate/methanol). 0.75 g of expected 3-[4-(4-methanesulfonylpiperazin-1-yl)phenyl]-3,8-diazabicyclo[3.2.1]-octane-8-carboxylic acid tert-butyl ester is obtained.

1. temperatureat reflux for 1 h 30
2. customAfter hydrolysis
3. extractionwith a saturated aqueous NaHCO3 solution, and extraction with ethyl acetate
4. washthe organic phase is washed with a saturated aqueous sodium chloride solution
5. dry with materialdried over MgSO4
6. customThe crude product obtained
7. customis chromatographed on silica gel, elution