Triethylaluminum → 4-[4-(5-Ethyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester

To a stirred solution of 4-[4-(5-Bromo-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.4 mmol) in anhydrous THF (4 mL) under N2 was added dichlorobis(tri-o-tolylphosphine)palladium(II) (14 mg, 0.02 mmol), CeCl3 (99 mg, 0.4 mmol) and AlEt3 (1M in hexanes, 1.5 mL, 1.2 mmol) and the reaction stirred at RT for 4 h. The reaction was quenched with ice, diluted with 0.5M aqueous Rochelle's salts (30 mL) and extracted with EtOAc (3×40 mL). The combined organics were washed with Rochelle's salts (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo and the crude residue purified by reverse phase preparative HPLC-MS to afford 4-[4-(5-ethyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester as an orange solid (83 mg, 61%).

1. customThe reaction was quenched with ice
2. additiondiluted with 0.5M aqueous Rochelle's salts (30 mL)
3. extractionextracted with EtOAc (3×40 mL)
4. washThe combined organics were washed with Rochelle's salts (2×50 mL), brine (50 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customthe crude residue purified by reverse phase preparative HPLC-MS

ORD-Eintrag

ord-3922b63dc8294e0e9990f9cad0c34368

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09193689B2