反应详情

1-Methanesulfonyl-4-[4-(4,4,5,5-tetramethyl[1,3,2]-dioxaborolan-2-yl)phenyl]-piperazine (1.8 g, 4.9 mmol) and 3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]-oct-2-ene-8-carboxylic acid tert-butyl ester (3.8 g, 5.9 mmol) are placed in 35 ml of DME and 6.14 ml of a 2N aqueous solution of K2CO3. After degassing with nitrogen, tetrakis(triphenylphosphine)palladium (1.136 g, 0.98 mmol) is added. The reaction medium is refluxed for 6 h. After hydrolysis and addition of ethyl acetate, the reaction medium is filtered on Celite®. The aqueous phase is then extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of NaHCO3 and than with water. After drying over MgSO4 and concentration to dryness, the crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of ethyl acetate in dichloromethane ranging from 0% to 20%. 0.83 g of 3-[4-(4-methanesulfonylpiperazin-1-yl)phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester is obtained.

1. additionis added
2. temperatureThe reaction medium is refluxed for 6 h
3. filtrationthe reaction medium is filtered on Celite®
4. extractionThe aqueous phase is then extracted with ethyl acetate
5. washThe organic phase is washed with a saturated aqueous solution of NaHCO3 and than with water
6. dry with materialAfter drying over MgSO4 and concentration to dryness
7. customthe crude product obtained
8. customis chromatographed on silica gel, elution