反应详情

An 8-mL vial containing a stir bar was charged with Pd2(dba)3 (0.01 equiv., 4 pmol, 4 mg.), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 1 (0.05 equiv., 0.02 mmol, 10 mg) and sodium t-butoxide (2.5 equiv., 1.03 mmol, 99 mg.). To this solution was transferred a solution of 6-chloro-2-(tetrahydro-pyran-4-yl)-3,4-dihydro-2H-isoquinolin-1-one (110 mg, 0.41 mmol) in anhydrous toluene (2 mL) under N2 with stirring at rt. Then, a solution of the (2S,3′S)-2-methyl-[1,3]-bipyrrolidinyl (1.3 equiv., 0.53 mmol, 83 mg) in anhydrous toluene (2 mL) was transferred. The vial was capped with a rubber septum, evacuated and backfilled with N2. To this vial was introduced 2 mL of anhydrous toluene. The reaction was heated in an oil bath set at 90° C. for 5 h, allowed to cool down to room temperature and quenched with water (2 mL). Extraction with ethyl acetate (3×10 mL) followed by chromatography on silica gel column with 0-5% 7N NH3/MeOH in DCM to give 85 mg (54% yield) of the title compound as a yellow solid.

1. additionAn 8-mL vial containing a stir bar
2. customThe vial was capped with a rubber septum
3. customevacuated
4. additionTo this vial was introduced 2 mL of anhydrous toluene
5. temperatureThe reaction was heated in an oil bath
6. temperatureto cool down to room temperature
7. customquenched with water (2 mL)
8. extractionExtraction with ethyl acetate (3×10 mL)